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Host range, host specificity and hypothesized host shift events among viruses of lower vertebrates


The successful replication of a viral agent in a host is a complex process that often leads to a species specificity of the virus and can make interspecies transmission difficult. Despite this difficulty, natural host switch seems to have been frequent among viruses of lower vertebrates, especially fish viruses, since there are several viruses known to be able to infect a wide range of species. In the present review we will focus on well documented reports of broad host range, variations in host specificity, and host shift events hypothesized for viruses within the genera Ranavirus, Novirhabdovirus, Betanodavirus, Isavirus, and some herpesvirus.

Table of Contents

  1. 1.


  2. 2.

    Ranaviruses - Interspecies and interclass transmission

  3. 3.

    Betanodaviruses - The role of mutation and reassortment in host specificity

  4. 4.

    Novirhabdoviruses - Infectious haematopoietic necrosis virus and viral haemorrhagic septicaemia virus, two different strategies within the same genus

  5. 5.

    Infectious salmon anaemia virus: Orthomyxoviruses "made for the change"

  6. 6.

    Herpesviruses: Very host specific viruses?

  7. 7.

    Aquabirnaviruses - Putative candidate for interspecies transmission but still not demonstrated

  8. 8.


  9. 9.

    Authors' contributions

  10. 10.

    Competing interests

1. Introduction

The successful replication of a viral agent in a host is a complex process which consists of a number of interactions, most of them related to the coevolution of pathogen and host. This coevolution often leads to a species specificity of the virus and can make interspecies transmission difficult. Therefore, natural host range switches by viruses are rare events. However, when they occur the results can become severe because the viruses may then spread widely through non previously adapted, and therefore immunologically naïve host populations.

Upon transmission to a new host species, viruses must usually adapt to a new genetic and immunologic environment in order to replicate and spread to other individuals within the species [1]. The high rates of mutation and replication of RNA viruses, such as human immunodeficiency virus (HIV) and influenza, facilitate the occurrence and fixation of those mutations that become beneficial under certain conditions [2]. Viral adaptations to new hosts primarily manifest as amino acid substitutions which can allow more efficient virus cell entry into the new host [3, 4], block interactions with detrimental host proteins [5, 6] or promote escape from both the new and the old host's immune responses [7, 8].

Influenza A is the paradigm of a virus capable of interspecies and interclass transmission. Those viruses are found in humans as well as in other animals, including swine, horses and birds, waterfowl being considered the natural reservoir [9]. Subtypes of Influenza A are distinguished by the two surface glycoproteins: haemagglutinin (HA) and neuraminidase (NA). Periodically a subtype of influenza can make the shift from aquatic birds to humans, possibly through an intermediate host, resulting in a widespread pandemic in an immunologically naïve population. These antigenic shifts can occur either through the transfer of an entire virus from one host to another or through a reassortment process where genomic segments of the avian virus mix with genomic segments of a virus currently circulating in humans.

A number of proteins have been implicated in determining host specificity of the virus. Influenza haemagglutinin binds to sialic acid linked to galactose on the surface of the targeted cell, and the differing nature of the sialic acid-galactose linkages in birds and humans provides an important barrier to host shift events. In this sense, a number of amino acid substitutions have been produced in influenza haemagglutinin to adjust to the different receptors [1014]. Neuraminidase, the protein responsible for cleaving the haemagglutinin from the receptor surface, also seems to be adapted to the particular sialic acid linkages [15]. Proteins in the viral replication complex (PA, PB1, PB2 and NP) have also been implicated in limiting host range by restricting replication and intra-host spread in mammals (for a review see [16]). In particular, a specific substitution in the PB2 gene has been identified as crucial for replication and intra-host spread in mammals [1719].

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from humans (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor binding domain of the S protein that were potentially important for SARS progression and tropism. It has been demonstrated that the double substitution of two amino acid residues of pcSARS-CoV for those of huSARS-CoV made pcSARS-CoV capable of infecting human cells [4], suggesting that these two residues are involved in the palm civet-human transmission.

Under certain circumstances, even a genetically stable DNA virus can gain the mutation required to adapt to a new host. That is the case of canine parvovirus (CPV) which emerged in 1978 as the cause of new enteric and myocardial diseases in dogs. The new virus spread globally in a pandemic and has since remained endemic in dogs throughout the world [20, 21]. Phylogenetic analysis showed that all CPV isolates obtained so far, termed CPV type 2, descended from a single ancestor closely related to the feline panleukopenia virus (FPV) which infects cats, mink and raccoons, but not dogs or cultured dog cells [21]. FPV and CPV type 2 isolates differ by as little as 0.5% in DNA sequence and it is possible that changes of only two amino acid residues in the capsid protein could have introduced the canine host range [22, 23]. During 1979 a CPV variant (CPV type 2a) emerged, spread worldwide within 1 year and replaced the CPV type 2 strain. CPV type 2a contained five substitutions in the capsid sequence compared to CPV type 2 and also infected and caused disease in cats [2426]. Therefore, the emergence of CPV seems to have been a multistep process, where a small number of mutations in the capsid protein gene allowed the virus to efficiently infect and spread within a new host order [27].

Viruses of lower vertebrates include a large number of viral agents, belonging to different viral families and genera, with RNA and DNA genomes, and displaying different host specificities. In fact, some viruses have a very narrow host range, whereas others are known to be able to infect a wide range of species. The wide host range suggests that, in any moment along the viral evolution, those viruses may have been involved in different host shift events. In the present review we will focus on well documented or hypothesized cases of host shift as well as variations in host range for the genera Ranavirus, Novirhabdovirus, Betanodavirus, Isavirus and several herpesvirus. However, the suspicion for interspecies transmission in other fish viruses remains.

2. Ranaviruses - Interspecies and interclass transmission

Iridoviruses are large double stranded DNA viruses with an icosahedral capsid ranging from 120 to 350 nm in diameter. Ranavirus is one of the five genera within the family Iridoviridae. Among the five genera, two contain viruses of invertebrates (genera Chloridiridovirus and Iridovirus), whereas the remaining three genera (Lymphocystivirus, Megalocytivirus and Ranavirus) contain viruses that infect lower vertebrates [28]. The family also includes several viruses than remain unassigned to any genus. None of the iridoviruses are known to infect homeothermic vertebrates. A variety of molecular characteristic such as GC content, nucleotide sequence and inferred amino acid sequence of key genes, such as the major capsid protein gene (MCP), can be used to distinguish genera and species within genera [29].

Although the disease was known before [30], the lymphocystis disease virus (LCDV), the first known iridovirus was discovered in 1962 [31]. Since then, iridoviruses have been linked to disease in frogs, salamanders and other amphibians, reptiles [29, 32], and more than 140 wild and cultured fish species in different parts of the world [29, 32, 33]. Interestingly, most of these fish iridoviruses have been shown to be more closely related to frog virus 3, the type species of the genus Ranavirus, than to Lymphocystivirus. In fact, ranaviruses have become important pathogens for cultured and wild finfish, not only due to the severity of the diseases that they cause but also because of their rapid global emergence in recent years [34].

Members of the genus Ranavirus infect vertebrates of three different taxonomic classes: amphibians, reptiles and fish [35]. Since the identification of epizootic hematopoietic necrosis virus (EHNV), first isolated from redfin perch [36] and the first iridovirus associated with epizootic mortality in vertebrates [37], ranaviruses have caused epizooties in other fish species: sheatfish and catfish in Europe [38], largemouth bass [39] and ornamental fish (imported from Asia) in the USA [40], as well as grouper cultured in Asia [41, 42]. In addition, ranaviruses have been isolated from diseased frogs, salamanders, turtles and snakes in different parts of the world [4347]. At present the International Committee on Taxonomy of Viruses [48] recognizes six species within the genus based on analysis of host range, sequence identity, and protein and RFLP profiles [49, 50], but there are also many additional isolates as well as a number of tentative species (Table 1). FV-3, EHNV, Bhole Iridovirus (BIV), Ambystoma tigrinum virus (ATV) and European catfish virus (ECV) are five closely-related viral species that share over 90% sequence identity within the MCP and other genes, but clearly differ from each other in host range and RFLP profiles. The sixth species is Santee-Cooper ranavirus (SCRV) that along with Singapore grouper iridovirus (SGIV), a tentative species, are the most divergent members of the genus. The MCP genes of these two viruses show approximately 80% and 70% sequence identity, respectively, with the MCP genes of the 5 other ranavirus species [51, 52].

Table 1 Ranaviruses recognised by the ICTV.

Several of these viruses have been demonstrated to have broad host specificity, suggesting the potential for interspecies and interclass transmission. A good example is BIV, which was isolated originally from diseased ornate burrowing frog (Limnodynastes ornatus) tadpoles in Australia [53] and has been shown experimentally to be pathogenic for other species of frog [54, 55], and also for a fish species, barramundi (Lates calcarifer) [56, 57]. Moreover, BIV has been associated with the "spinning tilapia" syndrome which causes epizootic mortalities in fry populations of tilapia (Oreochromis mossambicus) [56, 58]. A case of interspecies transmission was demonstrated by Cunningham et al. [59], who infected common frogs Rana temporaria with two ranavirus isolates obtained from diseased toads (Bufo bufo). In addition, apparently identical FV3 strains were isolated from dead or moribund free-living threespine stickleback fish (Gasterosteus aculeatus) and sympatric tadpoles of the red-legged frog (Rana aurora) [60], and FV3 and FV3-like viruses have been reported to infect sympatric amphibian species including ranid and hylid tadpoles, larval salamanders and newts [61]. Moreover, it has been experimentally demonstrated that FV3·is pathogenic for pike (Esox lucius) [62]. A very interesting case of cross-class infection was found studying ATV infection of salamanders. Phylogenetic analyses of sequence data from the MCP gene of ATV isolates from very different locations indicate that they are more closely related to fish ranaviruses, such as EHNV, than to other amphibian ranaviruses, such as FV3 [63]. These data suggested that ATV possibly originated via a host switch from fish, and was spread across North America due to the substantial trade of salamander larvae sold for bait [6365].

In a very recent and interesting study Jancovich et al. [66] obtained evidence for host shifts among ranaviruses and proposed that the ancestral ranavirus was a fish virus. Those authors performed a dot plot comparison of the EHNV genome with that of other ranaviruses previously sequenced (ATV, FV, TFV, Grouper iridovirus and SGIV) and the results obtained indicated that EHNV is more closely related to the amphibian ranaviruses than to the GIV-like viruses infecting fish, as shown by other phylogenetic analyses previously performed [67]. In fact, Jancovich et al. [66] observed two lineages, FV3/TFV (frog lineage) and EHNV/ATV (fish/salamander lineage), and the existence of two major genomic inversions that can be visualised on the dot plot. These inversions would correspond to rearrangements of segments in the FV3-like lineage, which means that EHNV/ATV is closer to the most recent common ancestor (MRCA) of ranaviruses. These authors postulate that there must have been at least three species jumps, from fish to frogs, from fish to salamanders and from frogs to reptiles, and perhaps as many as four species jumps, including a jump from tetrapod amphibians back to fish. A new ranavirus isolate obtained recently from dead wild edible frogs (Pelophylax esculentus) in Denmark, which showed a 98.8% nucleotide identity in the MCP gene with EHNV [68], would support that hypothesis.

It has been suggested that after the divergence into the salamander virus and frog virus lineages a subsequent host specific evolution could have occurred that would have limited cross transmission between both hosts, at least in laboratory infections [47]. However, there are some data that indicate that ranavirus transmission between these species occurs in nature. In this sense, an FV-3-like virus has been isolated from spotted salamander suffering from mortalities [69], and a model of FV3/FV3-like virus transmission in aquatic amphibian communities postulates that transmission of the virus occurs between anuran (i.e. frogs) and urodele (i.e. salamanders) species [61]. There is also some evidence that salamander ranavirus isolates are also isolated from or detected in laboratory-infected frogs [70].

3. Betanodaviruses - The role of mutation and reassortment in host specificity

Piscine nodaviruses belong to the genus Betanodavirus, within the family Nodaviridae[71]. Betanodaviruses are the aetiological agents of the disease known as viral nervous necrosis (VNN) or viral encephalopathy and retinopathy (VER), a devastating neuropathological condition that affects marine fish worldwide [72]. The affected fish developing clinical signs show abnormal swimming, neurological problems and buoyancy control loss.

The disease typically occurs in an outbreak form in larval and juvenile fish, and several species have been shown to be specially affected such as sea bass (Lates calcarifer and Dicentrarchus labrax), groupers (Epinephelus akaara, Epinephelus fuscogutatus, Epinephelus malabaricus, Epinephelus moara, Epinephelus septemfasciatus, Epinephelus tauvina, Epinephelus coioides and Cromileptes altivelis), striped jack (Pseudocaranx dentex), parrotfish (Oplegnathus fasciatus), tiger puffer (Takifugu rubripes), and flatfish (Verasper moseri, Hippoglossus hippoglossus, Paralichthys olivaceus, Scophthalmus maximus) [73]. The affected fish species and geographical ranges of clinical VNN described so far are provided in Table 2.

Table 2 Fish species affected -in natural infections- by viral nervous necrosis (VNN).

Betanodaviruses are small (25-30 nm), nonenveloped, icosahedral RNA viruses. The genome consists of two single stranded, positive-sense molecules. The larger genomic segment, RNA1 (3.1 kb), encodes the RNA dependent RNA polymerase (RdRp) of approximately 100 kDa, also named protein A [74, 75]. The smaller segment, RNA2 (1.4 kb), encodes the capsid protein of about 42 kDa [74, 76]. In addition, a subgenomic RNA3 is synthesised during RNA replication from the 3' terminus of RNA1.

Betanodaviruses have been classified into four genotypes, designated SJNNV (striped jack nervous necrosis virus), TPNNV (tiger puffer nervous necrosis virus), RGNNV (red grouper nervous necrosis virus) and BFNNV (barfin flounder nervous necrosis virus), using a partial sequence of RNA2, the T4 region, which is a highly variable region of around 400 nt [77, 78]. These types exhibit different capabilities for infecting fish species. Thus, RGNNV shows the broadest host range and causes disease in a variety of warm-water fish species, BFNNV is restricted to cold-water marine fish species and TPNNV infects only one species [72]. With regards to the SJNNV type, although for several years it was considered to be restricted to a few species present in Japanese waters [72, 78], in recent years it has been found in Senegalese sole Solea senegalensis[79, 80] as well as gilthead sea bream Sparus aurata and sea bass cultured in the Iberian Peninsula [79]. More recent studies [81] reported that most of the betanodavirus strains infecting Senegalese sole and gilthead sea bream, previously typed as SJNNV on the basis of the T4 region, were in fact RGNNV/SJNNV reassortants. Olveira et al. [81] observed that the reassortant strains exhibited a slightly modified SJNNV capsid, with three different amino acid positions in all strains (the differences increased to a maximum of six in some strains). One of these changes observed in residue 247 was encoded by the nucleotide triplet 737-739, which was included in the region between nucleotides 695 and 765, described previously by Ito et al. [82] as a host specificity determinant. Another change in the amino acid sequence at residue 270 was also observed on the C-terminal side of the capsid protein. These results confirmed that C-terminal protruding domains of the capsid protein are involved in host specificity, as reported previously by Iwamoto et al. [83] and Ito et al. [82]. It is well known that even a small number of amino acid substitutions in the capsid proteins can have dramatic effects on the host specificity of different animal viruses [84]. In this case, the changes observed in the SJNNV capsid seem to have allowed it to efficiently infect and spread within two new hosts, causing epizootic outbreaks in Senegalese sole and gilthead sea bream, which were not previously considered susceptible to SJNNV.

Other authors have also reported the existence of reassortants among betanodavirus isolates obtained from symptomatic sea bass harbouring an RNA1 segment of SJNNV type and an RNA2 of RGNNV type [85]. These data indicated that both combinations of genomic segments of SJNNV and RGNNV genotypes are successful and allow the resultant reassortant strains to produce disease. Interestingly, a certain relationship between the type of reassortant and the susceptible host species seems to exist: SJ/RG affecting sea bass and RG/SJ affecting Senegalese sole and gilthead sea bream.

Souto et al. [86] experimentally demonstrated the pathogenicity of the reassortant RG/SJ strains for Senegalese sole and compared it to that of the parental strains (RGNNV and SJNNV). Mortality was recorded only in the fish infected with the RG/SJ strains and betanodavirus were re-isolated from dead fish, fulfilling the River's postulates. However, virus was detected by RT-PCR and isolated from all pools of fish inoculated with RGNNV and SJNNV strains. These results indicate that both genotypes can replicate in Senegalese sole with no evident pathological effects and that the changes produced after the reassortment account for the pathogenicity for Senegalese sole.

4. Novirhabdoviruses - Infectious haematopoietic necrosis virus and viral haemorrhagic septicaemia virus, two different strategies within the same genus

Novirhabdovirus is one of the six established genera within the family Rhabdoviridae, and it is one of the two genera of this family known to infect aquatic animals (along with the Vesiculovirus genus). Two of the four recognised species of the genus are infectious haematopoietic necrosis virus (IHNV), the aetiological agent of infectious haematopoietic necrosis (IHN), and viral haemorrhagic septicaemia virus (VHSV), the causative agent of viral haemorrhagic septicaemia (VHS). Novirhabdovirus possess enveloped bullet-shaped virions. The viral genome consists of a linear non-segmented, negative-sense, single-stranded RNA of approximately 11 kilobases and contains 6 genes in the order 3'-N-P-M-G-NV-L-5' [87]. These viral species are quite different in terms of host range: quite narrow in the case of IHNV -apparently limited to salmonid fish-, and very broad for VHSV, including diverse fresh water and marine fish species.

IHNV is the type species for the genus Novirhabdovirus and it is one of the most serious viral pathogens of salmonid fish, infecting wild [88] and cultured salmonids in the USA, Europe and Asia [89]. The virus causes an acute systemic disease that can affect all five species of Pacific salmon (sockeye salmon Oncorhynchus nerka, pink salmon O. gurbuscha, chinook salmon O. tshawytscha, chum salmon O. keta, and coho salmon O. kisutch,) as well as Atlantic salmon (Salmo salar), and rainbow trout (O. mykiss) [89]. However, not all salmonid species are equally susceptible to IHNV [9093]. Garver et al. [90] have reported differences in susceptibility of sockeye salmon and rainbow trout to the different phylogenetic groups of IHNV established in North America (U, M and L) [94]. Isolates belonging to the U genogroup were highly virulent for sockeye salmon, while the M genogroup IHNV isolates were highly virulent for rainbow trout. Although not demonstrated, the U genogroup specificity for sockeye salmon is hypothesised to be associated with long-term coevolution of IHNV with sockeye salmon over centuries [90, 94]. In contrast to the U genogroup situation, the M genogroup specificity for rainbow trout may reflect a relatively recent host-parasite interaction. The origin of the M genogroup may have involved a host shift of the U genogroup IHNV from sockeye salmon to rainbow trout during the 1970s, followed by a relatively rapid evolution and divergence in rainbow trout [94, 95]. If this hypothesis is true, it would be interesting to know the mechanisms involved in the adaptation of the virus to the new host as this apparently caused a loss of virulence for its original host.

Until the mid-1980s, VHS was regarded as a disease affecting only rainbow trout and a few other freshwater fish species in aquaculture in continental Europe. Since then, however, VHSV has been isolated from a large range of free-living marine fish species, either diseased or asymptomatic, throughout the northern hemisphere. So far, VHSV has been isolated from more than 70 different fish species (for a review see references [96, 97]).

Different studies based on different gene sequences, including nucleoprotein (N), glycoprotein (N) and non-structural (NV) protein genes, have identified the existence of four genotypes of VHSV [98101]. Genotype I group isolates from continental Europe are pathogenic for rainbow trout, as well as several marine isolates from the Baltic sea; genotype II includes a number of marine isolates obtained from the Baltic sea with no clear link to rainbow trout aquaculture; genotype III comprises isolates from around the United Kingdom and the Flemish Cap area in the Northwestern Atlantic Ocean, and genotype IV includes VHSV strains isolated from Korea and Japan, both the Pacific and the Eastern coast of North America, and more recently the Great Lakes region.

The use of phylogenetic tools has provided considerable genetic evidence indicating that rainbow trout pathogenic VHSV emerged from a genotype I-type marine ancestor [98, 101103]. The shift could be explained by the occurrence of a single introduction or adaptation event followed by expansion of this "new" genotype virus within trout aquaculture [98, 101]. It has been suggested that the feeding of unpasteurised raw marine fish to farmed fish, a common practice in the early days of fish farming, could have been a likely route for the introduction of marine VHSV within rainbow trout aquaculture [104]. Only a limited number of amino acid residues might be involved in the determination of VHSV virulence for salmonids and this highlights the potential risk that marine strains may pose to freshwater aquaculture [105]. Snow & Cunningham [106] observed an increase in the virulence of the turbot isolate 860/94 following a number of passages in rainbow trout, although that increasing virulence was not accompanied by a difference in the consensus sequence in the glycoprotein.

Some phylogenetic studies indicate that VHSV may have been present in marine fish species in Europe for centuries and that the genotypes became separated a long time before fish farming was established in Europe and North America [107]. However, no isolates from wild marine fish were included in this study. Subsequent studies on molecular clocks supported this hypothesis and showed the existence of a molecular clock for European marine isolates without positive selection and a molecular clock for European freshwater isolates with positive selection [98]. In this sense, it has been estimated that the North American and European VHSV types diverged around the year 1500, and that the European freshwater and marine isolates diverged around 1950 [98].

In spite of the lack of reports on the definition of molecular determinants involved in host specificity, some studies performing comparative analysis of the complete genome sequences provide clues to the possible involvement of a small number of nucleotides [105, 108]. To demonstrate their implication in host specificity, the availability of infectious clones to generate recombinant IHNV and VHSV viruses will be helpful (see Biacchesi [109]).

5. Infectious salmon anaemia virus: Orthomyxoviruses "made for the change"

Infectious salmon anaemia virus (ISAV), the etiological agent of infectious salmon anaemia (ISA), is an RNA virus of the family Orthomyxoviridae, the only member of the genus Isavirus[110]. The genome of ISAV consists of eight segments of linear negative-sense single- stranded RNA. Viral particles are enveloped, with a diameter of 90-140 nm, and show surface projections consisting of a combined haemagglutinin-esterase (HE) protein encoded on segment 6 [111] and a separate fusion (F) protein encoded on segment 5 [112].

ISA is characterized by high mortality, and natural outbreaks have only been described in farmed Atlantic salmon. However, ISAV has been reported in both wild salmonid and non-salmonid fish [113115], and the virus may, under experimental conditions, persist and replicate in other salmonid (Salvelinus alpinus, O. mykiss, O. keta, O. kisutch) [116119] and non-salmonid fish (Clupea harengus, Gadus morhua) [120, 121].

The HE surface glycoprotein is the molecule with the highest sequence variability, and is assumed to be of importance in determining virulence. Most of the variation in this molecule is concentrated on a small highly polymorphic region (HPR). It is widely assumed that the source of the virulent ISAV isolates is an ISAV variant- designated HPR0- without any deletion in the HPR gene. The non-virulent nature of HPR0 viruses was indicated by the lack of disease in vivo and by their failure to replicate in cell culture [113, 122]. The widely held model suggests that virulent variants of the HPR0 archetype arise by deletion of several nucleotides in the HPR [113, 123, 124]. The driving forces behind the differential deletion patterns in the HPR could be analogous to a phenomenon described for Influenza A neuraminidase, where varying lengths of the stalk region have been reported, a property that was associated to host range adaptation [125, 126]. Following this theory and on the basis of a phylogenetic analysis of the HPR region, Mjaaland et al. [123] suggested that European ISA outbreaks may have been the result of several independent introductions of virus into farmed Atlantic salmon from wild fish, followed by adaptation to the new host through parallel but varied hemagglutinin gene deletions.

A recent study by Markussen et al. [127] has provided evidence for the role of recombination and reassortment in the evolution of ISAV. Those authors have demonstrated the existence of a new marker of virulence next to one of the two potential cleavage sites in the F protein and suggest that a single amino acid mutation may alter the recognition site, having a direct effect on the virulence of the virus. Markussen et al. [127] also suggested that the alterations at the cleavage site of the ISAV F protein together with deletions in the HPR region, most likely represent an adaptation of ISAV to Atlantic salmon from an unidentified reservoir, which leads to disease in densely populated fish farms.

However, Kibenge et al. [128] have postulated an alternative evolutionary model, which, in contrast to the widely accepted deletion theory, suggests that the original ancestral ISAV was virulent and that the insertion of specific motifs resulted in its attenuation. This last theory would not support a wild origin of ISAV because "wild" viruses are expected not to be as virulent as the farming-associated viruses. In natural conditions a balance between the virus and the host is expected to be maintained. However, this balance will be broken under intensive rearing conditions, conducive to an increase of virulence.

6. Herpesviruses: Very host specific viruses?

Herpesviruses (HVs) infect a wide variety of vertebrate hosts including mammals, birds, reptiles, amphibians and fish, and at least one invertebrate group, bivalve molluscs. HV share a characteristic virion structure, which consists of a large, linear, double-stranded DNA genome, an icosahedral capsid, a proteinaceous matrix (the tegument) and an envelope containing viral proteins [129].

HV taxonomy has recently undergone a revision by the ICTV [48], in which the previous family Herpesviridae was raised to the order Herpesvirales and split into three families: Herpesviridae, which divides into the subfamilies Alpha, Beta and Gammaherpesvirinae, containing mammalian, avian and reptilian viruses; Alloherpesviridae containing fish and amphibian viruses; and Malacoherpesviridae containing one single virus Ostreid herpesvirus (OsHV-1). Table 3 presents a list of fish and amphibian HV isolated in cell culture.

Table 3 Members of the family Alloherpesviridae and other fish herpesvirus isolated in cell culture.

As a general rule, the natural host range of mammalian and avian HV is highly restricted, and most herpesviruses are thought to have evolved in association with single host species [129], but exceptions have been reported among mammals [130]. On the basis of a comparative phylogenetic study of different hosts and fish herpesviruses, Waltzek et al. [131] indicate that some fish (salmonid, ictalurid and ciprinid) and ranid HV may have coevolved with their hosts, at least at the tips of the phylogenetic tree. However, the phylogenetic analysis revealed an overall discordance between HV and host lineages. One example of these discordances is provided by the family Acipenseridae (sturgeons), an ancient fish lineage and the sturgeon HV (AciHV1 and AciHV2) which are not sister taxa, with AciHV2 being the sister group of the ictalurid HV. Another example is provided by the eel HV (AngHV1), which grouped tightly with cyprinid HV. These authors suggested that the lack of cospeciation at deep nodes in the phylogenetic tree may indicate the existence of interspecies transmission.

There is clear evidence of interspecies transmission of OsHV-1 in marine bivalves [132, 133]. Although OsHV-1 was first isolated from the moribund larval Japanese oyster Crassostrea gigas, a variant of OsHV-1 (termed OsHV-1var) was detected in the Manila clam Ruditapes philipinarum[133] and subsequently in French scallops Pecten maximus[132].

7. Aquabirnaviruses - Putative candidate for interspecies transmission but still not demonstrated

Aquabirnavirus is one of the four genera of the family Birnaviridae. The type species of the genus is infectious pancreatic necrosis virus (IPNV), the first fish virus isolated and characterised in cell culture [134]. Aquabirnaviruses have a non-enveloped, icosahedral capsid approximately 60 nm in diameter containing a bisegmented, double-stranded RNA genome. The smaller genomic segment, segment B (2.8 kb), encodes the putative RNA-dependent RNA polymerase (VP1). The larger RNA segment (segment A; 3.1 kb) contains two partially overlapping open reading frames (ORF), a large ORF encoding the polyprotein and a small ORF encoding VP5 [135].

During the 1960's most of the reports on IPNV were associated with disease in juvenile salmonids. However, in the following years, isolations of aquatic birnaviruses were made from a large number of aquatic animals, most of them from animals with no evidence of disease, reaching 80 different species, including freshwater and marine species of fish and shellfish worldwide [136]. Although no studies have been performed on the capability of aquabirnaviruses for interspecies or interclass transmission, such events would explain their wide range of host species.

Most aquabirnaviruses are antigenically related and belong to serogroup A, which includes nine serotypes (A1-A9), whereas a few isolates represent an antigenically unrelated serogroup (serogroup B) [136, 137]. Six genogroups with a clear correspondence to the established serotypes have been identified [138, 139]. In addition, a seventh genogroup has been proposed [140] to include yellow tail ascites virus (YTAV), isolated in Japan from an epizootic in yellowtail (Seriola quinqueradiata) [141]. This genogroup also includes other birnavirus strains isolated from a variety of marine fish and molluscan shellfish in Japan, which have been tentatively named marine birnavirus (MABV) [142]. The high diversity of types of this virus could be a result of a long process of adaptation to new species. In addition, recently a molecular phenomenon was discovered among aquabirnaviruses, which could contributes to adaptation and replication in new hosts: natural reassortment. Thus, Romero-Brey et al. [143] in an analysis of IPNV-like strains isolated from different species of wild fish captured in the Flemish Cap, Newfoundland [144], reported the existence of natural reassortant strains harbouring a WB type segment A and Ab type segment B (WB/Ab reassortant). Subsequent studies on aquatic birnaviruses isolated from wild fish in Galician coastal waters (NW Spain) [145] confirmed the presence of natural reassortants of the same type in a larger proportion of the population than in the Flemish Cap. The lack of information about segment B of most aquabirnavirus isolates reported in the literature means it is not known if reassortment is a common phenomenon in nature. Putative involvement of genetic reassortment in the spreading of aquabirnaviruses and colonisation of such a high number of aquatic species seems an interesting topic to study.

8. Conclusions

The wide host range shown by many viruses affecting lower vertebrates is well known. In fact, for some of them -those historically most extensively studied- the list of susceptible species is surprisingly extensive. The best example are aquabirnaviruses. However, some others are only virulent to one or to a very narrow number of species. This diversity of host specificity patterns has not been well studied, and it is therefore poorly understood at present. In this sense, the status of knowledge varies dramatically among the different viral groups. In fact, for many of them only characterisation of field isolates has been performed, focusing on natural hosts, transmission pathways, genetic variation, etc. In a few cases, however, experimental studies have been conducted to document variations in host specificity between viral species (as for betanodaviruses) or between strains within a viral species (IHNV and VHSV). For some viruses, there is field data to support interspecies and interclass transmissions (ranavirus), for others, interspecies and interclass transmission is hypothesised based on phylogenetic relationships (novirhabdovirus, herpesvirus). For some, the molecular basis of host-specific virulence and/or host specificity has been investigated (ISAV, betanodavirus).

Compared with the examples from mammalian viruses described in the introduction, there are no absolutely certain examples of host shifts in fish viruses, but there are some that have been hypothesised based on reasonable evidence. The viruses tackled in this review are the few for which some information has been documented and is available at present, and could be summarised as follows.

Ranaviruses constitute a group of viruses with a broad host range, for which the interspecies and interclass transmission has been well documented; in addition, evidence for host shifts based on phylogenies and genome analyses is also available; however, to our knowledge, the molecular determinants and/or mechanisms for host-specificity have not been investigated.

A variation in host-specificity among the four viral genotypes of betanodaviruses is well documented. In addition, molecular determinants for their host specificity patterns have been investigated using natural reassortants and chimeric recombinant viruses. From these studies, specific amino acid changes have been identified as putatively associated with differences in host specificity.

In the case of novirhabdoviruses, variations in host specificity have been demonstrated among viral strains within both species -IHNV and VHSV-, although to a higher extent within VHSV. Although not scientifically demonstrated from a molecular basis, host shift/adaptation events could be hypothesised based on phylogenetic analyses. Moreover, whole genome sequence comparisons and infectious clones of IHNV and VHSV are now available, which are being used to study, and more deeply understand, host specificity determination in these viruses.

Several studies on the molecular basis of virulence of ISA virus have indicated that changes located in the haemagglutinin (HPR) and in the fusion protein are associated with outbreaks in Atlantic salmon. Based on phylogenetic analysis, it has been hypothesised that these changes could have been involved in a change in host specificity.

Phylogenetic analysis comparing fish herpesvirus and host lineages have revealed discordances that may suggest the existence of interspecies transmission. In addition, in mollusk bivalves there is field evidence of interspecies transmission of herpesviruses.

Finally, regarding aquabirnaviruses little information other than broad host range and diversity of IPNV (and aquabirnavirus in general) genogroups, has been reported. Similarly, there is no demonstration of variations in host specificity among different viral strains, and no studies on host specificity are available; the recently demonstrated occurrence of natural reassortment among field isolates could have some implication in determining the host specificity and virulence of these viruses, and will probably be investigated in the future.


  1. 1.

    Webby R, Hoffmann E, Webster R: Molecular constraints to interspecies transmission of viral pathogens. Nat Med. 2004, 10 (Suppl 12): S77-S81.

  2. 2.

    Moya A, Holmes EC, Gonzalez-Candelas F: The population genetics and evolutionary epidemiology of RNA viruses. Nat Rev Microbiol. 2004, 2: 279-288. 10.1038/nrmicro863.

  3. 3.

    Ito T, Couceiro JN, Kelm S: Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol. 1998, 72: 7367-7373.

  4. 4.

    Qu X-X, Hao P, Song X-J, Jiang S-M, Liu Y-X, Wang P-G, Rao X, Song H-D, Wang S-Y, Zuo Y, Zheng A-H, Luo M, Wang H-L, Deng F, Wang H-Z, Hu Z-H, Ding M-X, Zhao G-P, Deng H-K: Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for this variation in zoonotic tropism transition via a double substitution strategy. J Biol Chem. 2005, 280: 29588-29595. 10.1074/jbc.M500662200.

  5. 5.

    Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D: Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature. 2003, 424: 99-103. 10.1038/nature01709.

  6. 6.

    Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J: The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature. 2004, 427: 848-853. 10.1038/nature02343.

  7. 7.

    Smith DJ, Lapdes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA: Mapping the antigenic and genetic evolution of influenza virus. Science. 2004, 305: 371-376. 10.1126/science.1097211.

  8. 8.

    Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, Komarova NL, Nowak MA, Hahn BH, Kwong PD, Shaw GM: Antibody neutralization and escape by HIV-1. Nature. 2003, 422: 307-311. 10.1038/nature01470.

  9. 9.

    Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y: Evolution and ecology of influenza A viruses. Microbiol Rev. 1992, 56: 152-179.

  10. 10.

    Connor RJ, Kawaoka Y, Webster RG, Paulson JC: Receptor specificity in human, avian and equine H2 and H3 Influenza virus isolates. Virology. 1994, 205: 17-23. 10.1006/viro.1994.1615.

  11. 11.

    Matrosovich M, Tuzikov A, Bovin N, Gamabaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y: Early alterations of the receptor-binding properties of H1, H2 and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol. 2000, 74: 8502-8512. 10.1128/JVI.74.18.8502-8512.2000.

  12. 12.

    Nobusawa E, Aoyama T, Kato H, Suzuki Y, Tateno Y, Nakajima K: Comparison of complete amino-acid-sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza a-viruses. Virology. 1991, 182: 475-485. 10.1016/0042-6822(91)90588-3.

  13. 13.

    Rogers GN, Paulson JC, Daniels RS, Skehel JJ, Wilson IA, Wiley DC: Single amino-acid substitutions in Influenza hemagglutinin change receptor-binding specificity. Nature. 1983, 304: 76-78. 10.1038/304076a0.

  14. 14.

    Vines A, Wells K, Matrosovich M, Castrucci MR, Ito T, Kawaoka Y: The role of influenza a virus hemagglutinin residues 226 and 228 in receptor specificity and host range restriction. J Virol. 1998, 72: 7626-7631.

  15. 15.

    Baigent SJ, McCauley JW: Influenza type A in humans, mammals and birds: determinants of virus virulence, host range and interspecies transmission. Bioessays. 2003, 25: 657-671. 10.1002/bies.10303.

  16. 16.

    Naffakh N, Tomoiu A, Rameix-Welti MA, van der Werf S: Host restriction of avian influenza viruses at the level of the ribonucleoproteins. Annu Rev Microbiol. 2008, 62: 403-424. 10.1146/annurev.micro.62.081307.162746.

  17. 17.

    Hatta M, Gao P, Halfmann P, Kawaoka Y: Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science. 2001, 293: 1840-1842. 10.1126/science.1062882.

  18. 18.

    Steel J, Lowen A, Mubareka S, Pales P, Baric R: Transmission of influenza virus in a mammalian host is increase by PB2 amino acids 627K or 627E/701N. PLoS Pathog. 2009, 5: e10000252-

  19. 19.

    Subbaran EK, London W, Murphy BR: A single amino-acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol. 1993, 67: 1761-1764.

  20. 20.

    Parrish CR: Emergence, natural history, and variation of canine, mink and feline parvovirus. Adv Virus Res. 1990, 38: 402-450.

  21. 21.

    Truyen U, Gruenberg A, Chang SF, Obermaier B, Veijalainen P, Parrish CR: Evolution of the feline subgroup parvoviruses and the control of canine host range in vivo. J Virol. 1995, 69: 4792-4710.

  22. 22.

    Chang SG, Sgro JY, Parrish CR: Multiple amino acids in the capsid structure of canine parvovirus coordinately determine the canine host range and specific antigenic and hemagglutination properties. J Virol. 1992, 66: 6858-6867.

  23. 23.

    Horiuchi M, Goto H, Ishiguro N, Shinagawa M: Mapping of determinants of the host range for canine cells in the genome of canine parvovirus using canine parvovirus/mink enteritis virus chimeric viruses. J Gen Virol. 1994, 75: 1319-1328. 10.1099/0022-1317-75-6-1319.

  24. 24.

    Parrish CR, Have P, Foreyt WJ, Evermann JF, Senda M, Carmichael LE: The global spread and replacement of canine parvovirus strains. J Gen Virol. 1988, 69: 1111-1116. 10.1099/0022-1317-69-5-1111.

  25. 25.

    Parrish C, Aquadro C, Strassherim ML, Evermann JF, Sgro JY, Mohammed H: Rapid antigenic-type replacement and DNA sequence evolution of canine parvovirus. J Virol. 1991, 65: 6544-6552.

  26. 26.

    Truyen U, Evermann JF, Vieler E, Parrish CR: Evolution of canine parvovirus involved loss and gain of feline host range. Virology. 1996, 215: 186-189. 10.1006/viro.1996.0021.

  27. 27.

    Hueffer K, Parker JSL, Weichert WS, Geisel RE, Sgro JY, Parrish CR: The natural host range shift and subsequent evolution of canine parvovirus resulted from virus-specific binding to the canine transferring receptor. J Virol. 2003, 77: 1718-1726. 10.1128/JVI.77.3.1718-1726.2003.

  28. 28.

    Chinchar GD, Essbauer S, He JG, Hyatt A, Miyazaki T, Seligy V, Williams T: Family Iridoviridae. Virus Taxonomy. Edited by: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. 2005, 8th Report ICTV, Elsevier Academic Press, San Diego, CA, 145-158.

  29. 29.

    Williams T, Barbosa-Solomieu V, Chinchar VG: A decade of advances in iridovirus research. Adv Virus Res. 2005, 65: 173-248.

  30. 30.

    Watson SW: Virus Diseases of Fish. Trans Am Fish Soc. 1954, 83: 331-341. 10.1577/1548-8659(1953)83[331:VDOF]2.0.CO;2.

  31. 31.

    Walker R: Fine structure of lymphocystis virus of fish. Virology. 1962, 18: 503-505. 10.1016/0042-6822(62)90047-8.

  32. 32.

    Whittington RJ, Becker JA, Dennis MM: Iridovirus infections in finfish-critical review with emphasis on ranaviruses. J Fish Dis. 2010, 33: 95-122. 10.1111/j.1365-2761.2009.01110.x.

  33. 33.

    Essbauer S, Ahne W: Viruses of lower vertebrates. J Vet Med B Infect Dis Vet Public Health. 2001, 48: 403-475.

  34. 34.

    Schloegel LM, Daszak P, Cunningham AA, Speare R, Hill B: Two amphibian diseases, chytridiomycosis and ranaviral disease, are now globally notifiable to the World Organization for Animal Health (OIE): an assessment. Dis Aquat Organ. 2010, 92: 101-108. 10.3354/dao02140.

  35. 35.

    Chinchar GD: Ranaviruses (family Iridoviridae): Emerging cold-blooded killers. Arch Virol. 2002, 147: 447-470. 10.1007/s007050200000.

  36. 36.

    Langdon JS, Humphrey JL, Williams LM, Hyatt AD, Westbury HA: 1st virus isolation from Australian fish-an iridoviurs-like pathogen from redfin perch, Perca fluviatilis L. J Fish Dis. 1986, 9: 263-268. 10.1111/j.1365-2761.1986.tb01011.x.

  37. 37.

    Langdon JS, Humphrey JL, Williams LM: Outbreaks of an EHNV-like iridovirus in cultured rainbow trout in Salmo gairdneri Richardson in Australia. J Fish Dis. 1988, 11: 93-96. 10.1111/j.1365-2761.1988.tb00527.x.

  38. 38.

    Ahne W, Brémont M, Hedrick RP, Hyatt AD, Whittington RJ: Iridoviruses associated with epizootic haematopoietic necrosis (EHN) in aquaculture. World J Microbiol Biotechnol. 1997, 13: 367-373. 10.1023/A:1018563930712.

  39. 39.

    Plumb JA, Grizzle JM, Young HE, Noyes AD: An iridovirus isolated from wild largemouth bass. J Aquat Anim Health. 1996, 8: 265-270. 10.1577/1548-8667(1996)008<0265:AIIFWL>2.3.CO;2.

  40. 40.

    Hedrick RP, McDowell TS: Properties of iridoviruses from ornamental fish. Vet Res. 1995, 26: 423-427.

  41. 41.

    Chua FHC, Ng ML, Ng KL, Loo JJ, Wee JY: Investigation of outbreaks of novel disease, "sleepy grouper disease" affecting the brown-spotted grouper Epinephelus tauvina Forskal. J Fish Dis. 1994, 17: 417-427. 10.1111/j.1365-2761.1994.tb00237.x.

  42. 42.

    Qin QW, Chang SF, Ngoh-Lim GH, Gibson-Kueh S, Shi C, Lam TJ: Characterization of a novel ranavirus isolated from grouper Epinephelus tauvina. Dis Aquat Organ. 2003, 53: 1-9.

  43. 43.

    Benetka V, Grabensteiner E, Gumpenberger M, Neubauer C, Hirschmüller B, Möstl K: First report of an iridovirus (Genus Ranavirus) infection in a Leopard tortoise (Ceochelone pardalis pardalis). Vet Med Austria. 2007, 94: 243-248.

  44. 44.

    Bollinger TK, Mao J, Schock D, Brigham RM, Chinchar BG: Pathology, isolation and molecular characterization of an iridovirus from tiger salamanders in Saskatchewan. J Wildl Dis. 1999, 35: 413-429.

  45. 45.

    Hyatt AD, Williamson M, Coupar BE, Middleton D, Hengstberger SG, Gould AR, Selleck P, Wise TG, Kattenbelt J, Cunningham AA, Lee J: First identification of a ranavirus from green pythons (Chondropython viridis). J Wildl Dis. 2002, 38: 239-252.

  46. 46.

    Jancovich JK, Davidson EW, Morado JF, Jacobs BL, Collins JP: Isolation of a lethal virus form the endangered tiger salamander Ambystoma tigrinum tebbinsi. Dis Aquat Organ. 1997, 31: 161-167.

  47. 47.

    Marschang RE, Becher P, Posthaus H, Wild P, Thiel HJ: Isolation and characterization of an iridovirus from Hermans tortoises (Testudo hermanni). Arch Virol. 1999, 144: 1909-1922. 10.1007/s007050050714.

  48. 48.

    International Committee on Taxonomy of Viruses. []

  49. 49.

    Hyatt AD, Gould AR, Zupanovic Z, Cunningham AA, Hengstberger S, Whittington RJ, Kattenbelt J, Coupar BE: Comparative studies of piscine and amphibian iridoviruses. Arch Virol. 2000, 145: 303-331.

  50. 50.

    Mao J, Hedrick RP, Chinchar VG: Molecular characterization, sequence analysis and taxonomic position of newly isolated fish iridoviruses. Virology. 1997, 229: 212-220. 10.1006/viro.1996.8435.

  51. 51.

    Mao J, Wang J, Chinchar GD, Chinchar VG: Molecular characterization of a ranavirus isolated form largemouth bass Micropterus salmoides. Dis Aquat Organ. 1999, 37: 107-114.

  52. 52.

    Ting JW, Wu MF, Tsai CT, Lin CC, Guo IC, Chang CY: Identification and characterization of a novel gene of grouper iridovirus encoding a purine nucleoside phosphorylase. J Gen Virol. 2004, 85: 2883-2892. 10.1099/vir.0.80249-0.

  53. 53.

    Speare R, Smith J: An iridovirus-like agent isolated from the ornate burrowing frog Lymnodynastes ornatus in northern Australia. Dis Aquat Organ. 1992, 14: 51-57.

  54. 54.

    Cullen BR, Owens L, Wittington RJ: Experimental infection of Australian anurans (Limnodynastes terraereginae and Litoria latopalmata) with Bohle iridovirus. Dis Aquat Organ. 1995, 23: 83-92.

  55. 55.

    Cullen BR, Owens L: Experimental challenge and clinical cases of Bohle iridovirus (BIV) in native Australian anurans. Dis Aquat Organ. 2002, 49: 83-92.

  56. 56.

    Ariel E, Owens L: Epizootic mortalities in tilapia Oreochromis mossambicus. Dis Aquat Organ. 1997, 29: 1-6.

  57. 57.

    Moody NJG, Owens L: Experimental demonstration of pathogenicity of a frog virus, bohle iridovirus, for a fish species, barramudi Lates calcarifer. Dis Aquat Organ. 1994, 18: 95-102.

  58. 58.

    McGrogan DG, Ostland VE, Byrne PJ, Ferguson HW: Systemic disease involving an iridovirus-like agent in cultured tilapia, Oreochromis niloliticus L.-a case report. J Fish Dis. 1998, 21: 149-152. 10.1046/j.1365-2761.1998.00082.x.

  59. 59.

    Cunningham AA, Hyatt AD, Russell P, Bennet PM: Experimental transmission of ranavirus disease of common toads (Bufo bufo) to common frogs (Rana temporaria). Epidemiol Infect. 2007, 135: 1213-1216.

  60. 60.

    Mao J, Green DE, Fellers G, Chinchar VG: Molecular characterization of iridoviruses isolated from sympatric amphibians and fish. Virus Res. 1999, 63: 45-62. 10.1016/S0168-1702(99)00057-X.

  61. 61.

    Duffus ALJ, Pauli BD, Woxney K, Brunetti CR, Berrill M: Frog Virus 3-like infections in aquatic amphibian communities. J Wildl Dis. 2008, 44: 109-120.

  62. 62.

    Bang Jensen B, Kjær Ersbøll A, Ariel E: Susceptibility of pike Esox lucius to a panel of Ranavirus isolates. Dis Aquat Organ. 2009, 83: 169-179.

  63. 63.

    Jancovich JK, Davidson EW, Parameswaran N, Mao J, Chinchar VG, Collins JP, Jacobs BL, Storfer A: Evidence for emergence of an anphibian iridoviral disease because of human-enhanced spread. Mol Ecol. 2005, 14: 213-224.

  64. 64.

    Picco AM, Collins JP: Amphibian commerce as a likeky source of pathogen pollution. Conserv Biol. 2008, 22: 1582-1589. 10.1111/j.1523-1739.2008.01025.x.

  65. 65.

    Schloegal LM, Picco AM, Lilpatrick AM, Davies AJ, Hyatt AD: Magnitude of the US trade in amphibians and presence of Batrachochytrium dendrobatidis and ranavirus infection in imported North American bullfrogs (Rana catesbeiana). Biol Conserv. 2009, 142: 1420-1426. 10.1016/j.biocon.2009.02.007.

  66. 66.

    Jancovich JK, Brémont M, Touchman JF, Jacobs BL: Evidence for multiple recent host species shifts among the ranaviruses (family Iridoviridae). J Virol. 2010, 84: 2636-2647. 10.1128/JVI.01991-09.

  67. 67.

    Holopainen R, Ohlemeyer S, Schütze H, Bergmann SM, Tapiovaara H: Ranavirus phylogeny and differentiation based on major capsid protein, DNA polymerase and neurofilament triplet H1-like protein genes. Dis Aquat Organ. 2009, 85: 81-91.

  68. 68.

    Ariel E, Kielgast J, Svart HE, Larsen K, Tapiovaara H, Jensen BB, Holopainen R: Ranavirus in wild edible frogs Pelophylax kl. esculentus in Denmark. Dis Aquat Organ. 2009, 85: 7-14.

  69. 69.

    Docherty DE, Meteyer CU, Wang J, Mao J, Case ST, Chinchar VG: Diagnostic and molecular evaluation of three iridovirus-associated salamander mortality events. J Wildl Dis. 2003, 39: 556-566.

  70. 70.

    Schock DM, Bollinger TK, Chinchar VG, Jancovich JK, Collins JP: Experimental evidence that amphibian ranaviruses are multi-host pathogens. Copeia. 2008, 2008: 133-143. 10.1643/CP-06-134.

  71. 71.

    Schneemann A, Ball LA, Delsert C, Johnson JE, Nishizawa T: Family Nodaviridae. Virus Taxonomy. 8th Report ICTV. Edited by: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. 2005, Elsevier Academic Press, San Diego, CA, 865-872.

  72. 72.

    Munday B, Kwang J, Moody N: Betanodavirus infections of teleost fish: a review. J Fish Dis. 2002, 25: 127-142. 10.1046/j.1365-2761.2002.00350.x.

  73. 73.

    OIE (Office International des Epizooties): Manual of Diagnostic Tests for Aquatic Animals. 2003, OIE, Paris, Manual, Chapter 2.1.7. Viral encephalopathy and retinopathy,, 4

  74. 74.

    Nagai T, Nishizawa T: Sequence of the non-structural protein gene encoded by RNA1 of striped jack nervous necrosis virus. J Gen Virol. 1999, 80: 3019-3022.

  75. 75.

    Tan C, Huang B, Chang S, Ngoh G, Munday B, Che S, Kwang J: Determination of the complete nucleotide sequences of RNA1 and RNA2 from greasy grouper (Epinephelus tauvina) nervous necrosis virus, Singapore strain. J Gen Virol. 2001, 82: 647-653.

  76. 76.

    Delsert C, Morin N, Comps M: A fish encephalitis virus that differs from other nodaviruses by its capsid protein processing. Arch Virol. 1997, 142: 2359-2371. 10.1007/s007050050248.

  77. 77.

    Nishizawa T, Mori K, Furuhashi M, Nakai T, Furusawa I, Muroga K: Comparison of the coat protein genes of five fish nodaviruses, the causative agents of nervous necrosis in marine fish. J Gen Virol. 1995, 76: 1563-1569. 10.1099/0022-1317-76-7-1563.

  78. 78.

    Nishizawa T, Furuhashi M, Nagai T, Nakai T, Muroga K: Genomic classification of fish nodaviruses by molecular phylogenetic analysis of the coat protein gene. Appl Environ Microbiol. 1997, 63: 1633-1636.

  79. 79.

    Cutrín JM, Thiéry R, Leao P, Olveira JG, Barja JL, Bandín I: Emergence of pathogenic betanodaviruses belonging to SJNNV genogroup in farmed fish species from the Iberian Peninsula. J Fish Dis. 2007, 30: 225-222. 10.1111/j.1365-2761.2007.00803.x.

  80. 80.

    Thiéry R, Cozien J, de Boisséson C, Kerbat-Boscher S, Névarez L: Genomic classification of new betanodaviruses isolates by phylogenetic analysis of the coat protein gene suggests a low host-fish species specificity. J Gen Virol. 2004, 85: 3079-3087. 10.1099/vir.0.80264-0.

  81. 81.

    Olveira JG, Souto S, Dopazo CP, Thiéry R, Barja JL, Bandín I: Comparative analysis of both genomic segments of betanodaviruses isolated from epizootic outbreaks in farmed fish species provides evidence for genetic reassortment. J Gen Virol. 2009, 90: 2940-2951. 10.1099/vir.0.013912-0.

  82. 82.

    Ito Y, Okinaka Y, Mori K-I, Sugaya T, Nishioka T, Oka M, Nakai T: Variable region of betanodavirus RNA2 is sufficient to determine host specificity. Dis Aquat Organ. 2008, 79: 199-205.

  83. 83.

    Iwamoto T, Okinaka Y, Mise K, Mori K-I, Arimoto M, Okuno T, Nakai T: Identification of host-specificity determinants in betanodaviruses by using reassortants between striped jack nervous necrosis virus and sevenband grouper nervous necrosis virus. J Virol. 2004, 78: 1256-1262. 10.1128/JVI.78.3.1256-1262.2004.

  84. 84.

    Baranowski E, Ruiz-Jarabo CM, Domingo E: Evolution of cell recognition by viruses. Science. 2001, 292: 1102-1105. 10.1126/science.1058613.

  85. 85.

    Toffolo V, Negrisolo E, Maltese C, Bovo G, Belvedere P, Colombo L, Dalla Valle L: Phylogeny of betanodaviruses and molecular evolution of their RNA polymerase and coat proteins. Mol Phylogenet Evol. 2007, 4: 298-308.

  86. 86.

    Souto S, Olveira JG, Dopazo CP, Barja JL, Bandín I: Betanodavirus infection in Senegalese sole: the role of reassortment. 8th Int. Symp. 2010, Viruses of Lower Vertebrates, Santiago de Compostela, Spain, 83-

  87. 87.

    Tordo N, Benmansour A, Calisher C, Dietzgen RC, Fang R-X, Jackson AO, Kurath G, Nadin-Davis S, Tesh RB, Walker PJ: Family Rhabdoviridae Genus Novirhabdovirus. Virus Taxonomy. 8th Report ICTV. Edited by: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. 2005, Elsevier Academic Press, San Diego, CA, 635-636.

  88. 88.

    Williams IV, Amend DF: A natural epizootic of infectious hematopoietic necrosis in fry of sockeye salmon (Onchorhynchus nerka) at Chilko Lake, British Columbia. J Fish Res Board Can. 1976, 33 (7): 1564-1567. 10.1139/f76-196.

  89. 89.

    Bootland LM, Leong JC: Infectious hematopoietic necrosis virus. Edited by: Woo PTK, Bruno DW. 1999, CAB International, New York, 57-121. Fish diseases and disorders, volume 2

  90. 90.

    Garver KA, Batts WN, Kurath G: Virulence comparisons of infectiuous hematopoietic necrosis virus U and M genogruoups in sockeye salmon and rainbow trout. J Aquat Anim Health. 2006, 18: 232-243. 10.1577/H05-038.1.

  91. 91.

    LaPatra SE: Factors affecting pathogenicity of infectious hematopoietic necrosis virus (IHNV) for salmonid fish. J Aquat Anim Health. 1998, 10: 121-131. 10.1577/1548-8667(1998)010<0121:FAPOIH>2.0.CO;2.

  92. 92.

    LaPatra SE, Fryer JL, Rohovec JS: Virulence comparison of different electropherotypes of infectious hematopoietic necrosis virus. Dis Aquat Organ. 1993, 16 (2): 121-131.

  93. 93.

    LaPatra SE, Grober WJ, Rohovec JS, Fryer JL: Size related susceptibility of salmonids to two strains of infectious hematopoietic necrosis virus. Trans Am Fish Soc. 1990, 119 (1): 25-30. 10.1577/1548-8659(1990)119<0025:SSOSTT>2.3.CO;2.

  94. 94.

    Kurath G, Garver KA, Troyer RM, Emmenegger EJ, Einer Jensen K, Anderson ED: Phylogeography of infectious hematopoietic necrosis virus in North America. J Gen Virol. 2003, 84: 803-814. 10.1099/vir.0.18771-0.

  95. 95.

    Troyer RM, Kurath G: Molecular epidemiology of infectious hematopoietic necrosis virus reveals complex virus traffic and evolution within southern Idaho aquaculture. Dis Aquat Organ. 2003, 55: 175-185.

  96. 96.

    Skall HF, Olesen NJ, Mellergaard S: Viral haemorrhagic septicaemia virus in marine fish and its implications for fish farming - a review. J Fish Dis. 2005, 28: 509-529. 10.1111/j.1365-2761.2005.00654.x.

  97. 97.

    OIE (Office International des Epizooties): Manual of Diagnostic Tests for Aquatic Animals. 2010, Paris, Chapter 2.3.9. Viral haemorrhagic septicaemia virus, OIE (on line edition, []

  98. 98.

    Einer-Jensen K, Ahrens P, Forsberg R, Lorenzen N: Evolution of the fish rhabdovirus viral haemorrhagic septicaemia virus. J Gen Virol. 2004, 85: 1167-1179. 10.1099/vir.0.79820-0.

  99. 99.

    Einer-Jensen K, Ahrens P, Lorenzen N: Parallel phylogenetic analyses using the N, G or Nv gene from a fixed group of VHSV isolates reveal the same overall genetic typing. Dis Aquat Organ. 2005, 67: 39-45.

  100. 100.

    Snow M, Cunningham CO, Melvin WT, Kurath G: Analysis of the nucleoprotein gene identifies distinct lineages of viral haemorrhagic septicaemia virus within the European marine environment. Virus Res. 1999, 63: 35-44. 10.1016/S0168-1702(99)00056-8.

  101. 101.

    Snow M, Bain N, Black J, Taupin V, Cunningham CO, King JA, Skall HF, Raynard RS: Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Dis Aquat Organ. 2004, 61: 11-21.

  102. 102.

    Dixon PF: VHSV came from the marine environment: clues from the literature, or just red herrings?. Bull Eur Ass Fish Path. 1999, 19: 60-65.

  103. 103.

    Stone DM, Way K, Dixon PF: Nucleotide sequence of the glycoprotein gene of viral haemorrhagic septicaemia (VHS) viruses from different geographical areas: a link between VHS in farmed fish species and viruses isolated from North Sea cod (Gadus morhua L.). J Gen Virol. 1997, 78: 1319-1326.

  104. 104.

    Meyers TR, Winton JR: Viral hemorrhagic septicemia in North America. Annu Rev Fish Dis. 1995, 5: 3-24.

  105. 105.

    Betts AM, Stone DM: Nucleotide sequence analysis of the entire coding regions of virulent and avirulent strains of viral haemorrhagic septicaemia virus. Virus Genes. 2000, 20: 259-262. 10.1023/A:1008148813746.

  106. 106.

    Snow M, Cunningham CO: Virulence and nucleotide sequence analysis of marine viral haemorrhagic septicaemia virus following in vivo passage in rainbow trout Onchorhynchus mykiss. Dis Aquat Organ. 2000, 42: 17-26.

  107. 107.

    Benmansour A, Basurco B, Monnier AF, Vende P, Winton JR, de Kinkelin P: Sequence variation of the glycoprotein gene identifies three distinct lineages within field isolates of viral haemorrhagic septicaemia virus, a fish rhabdovirus. J Gen Virol. 1997, 78: 2837-2846.

  108. 108.

    Campbell S, Collet B, Einer-Jensen K, Secombes CJ, Snow M: Identifying potential virulence determinants in viral haemorrhagic septicaemia virus (VHSV) for rainbow trout. Dis Aquat Organ. 2009, 86: 205-212.

  109. 109.

    Biacchesi S: The reverse genetics applied to fish RNA viruses. Vet Res. 2011, 42: 12-10.1186/1297-9716-42-12.

  110. 110.

    Kawaoka Y, Cox NJ, Haller O, Hongo S, Kaverin N, Klenk H-D, Lamb RA, McCauley J, Palese P, Rimstad E, Webster RG: Genus Isavirus. Virus Taxonomy. 8th Report ICTV. Edited by: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. 2005, Elsevier Academic Press, San Diego, CA, 681-693.

  111. 111.

    Falk K, Aspehaug V, Vlasak R, Edresen C: Identification and characterization of a viral structural proteins of infectious salmon anemia virus. J Virol. 2004, 78: 3063-3071. 10.1128/JVI.78.6.3063-3071.2004.

  112. 112.

    Aspehaug VT, Mikalsen AB, Snow M, Biering E, Villoing S: Characterization of the infectious salmon anemia virus fusion protein. J Virol. 2005, 79: 12544-12553. 10.1128/JVI.79.19.12544-12553.2005.

  113. 113.

    Cunningham CO, Gregory A, Black J, Simpson I, Raynard RS: A novel variant of infectious salmon anaemia virus (ISAV) haemagglutinin gene suggests mechanisms for virus diversity. Bull Eur Ass Fish Pathol. 2002, 22: 366-374.

  114. 114.

    Plarre H, Devold M, Snow M, Nylund A: Prevalence of infectious salmon anaemia virus (ISAV) in wild salmonids in western Norway. Dis Aquat Organ. 2005, 66: 71-79.

  115. 115.

    Raynard RS, Murray AG, Gregory A: Infectious salmon anaemia virus in wild fish from Scotland. Dis Aquat Organ. 2001, 46: 93-100.

  116. 116.

    Nylund A, Alexandersen S, Jakobsen P, Rolland JB: Infectious salmon anemia (ISA) in brown trout. J Aquat Anim Health. 1995, 7: 236-240. 10.1577/1548-8667(1995)007<0236:ISAVII>2.3.CO;2.

  117. 117.

    Nylund A, Kvenseth AM, Krossøy B, Hodneland K: Replication of the infectious salmon anaemia virus (ISAV) in rainbow trout (Oncorhynchus mykiss, Walbaum, 1792). J Fish Dis. 1997, 20: 275-279. 10.1046/j.1365-2761.1997.00300.x.

  118. 118.

    Rolland JB, Winton JR: Relative resistance of Pacific salmon to infectious salmon anaemia virus. J Fish Dis. 2003, 26: 511-520. 10.1046/j.1365-2761.2003.00473.x.

  119. 119.

    Snow M, Raynard R, Bruno DW: Comparative susceptibility of Arctic char (Salvelinus alpinus), rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta) to the Scottish isolate of infectious salmon anaemia virus. Aquaculture. 2001, 196: 47-54. 10.1016/S0044-8486(00)00588-3.

  120. 120.

    Grove S, Hjortaas MJ, Reitan LJ, Dannevig BH: Infectious salmon anaemia virus (ISAV) in experimentally challenged Atlantic cod (Gadus morhua). Arch Virol. 2007, 152: 1829-1837. 10.1007/s00705-007-1016-z.

  121. 121.

    Nylund A, Devold M, Mullins J, Plarre H: Herring (Clupea harengus): a host for infectious salmon anaemia virus (ISAV). Bull Eur Assoc Fish Pathol. 2002, 22: 311-318.

  122. 122.

    Cook-Versloot M, Griffiths S, Cusack R, McGeachy S, Ritchie R: Identification and characterization of infectious salmon anemia virus (ISAV) hemagglutinin gene highly polymorphic region (HPR) type 0 in North America. Bull Eur Ass Fish Pathol. 2004, 24: 203-208.

  123. 123.

    Mjaaland S, Hungnes O, Teig N, Dannevig BH, Thorud K, Rimstad E: Polymorphism in the infectious salmon anemia virus hemagglutinin gene: importance and possible implications for evolution and ecology of infectious salmon anemia disease. Virology. 2002, 304: 379-391. 10.1006/viro.2002.1658.

  124. 124.

    Nylund A, Devold M, Plarre H, Isdal E, Aarseth M: Emergence and maintenance of infectious salmon anemia virus (ISAV) in Europe: a new hypothesis. Dis Aquat Organ. 2003, 56: 11-24.

  125. 125.

    Air GM, Laver WG, Luo M, Stray SJ, Legrone G, Wbster RG: Antigenic, sequence, and crystal variation in influenza B neuraminidase. Virology. 1990, 177: 578-587. 10.1016/0042-6822(90)90523-T.

  126. 126.

    Castrucci MR, Kawaoka Y: Biologic importance of neuraminidase stalk length in influenza A virus. J Virol. 1993, 113: 725-735.

  127. 127.

    Markussen T, Monceyron Jonassen C, Numanovic S, Braanen S, Hjortaas M, Nilsen H, Mjaalanad S: Evolutionary mechanisms involved in the virulence of infectious salmon anaemia virus (ISAV), a piscine orthomyxovirus. Virology. 2008, 374: 515-527. 10.1016/j.virol.2008.01.019.

  128. 128.

    Kibenge FSB, Kibenge MJT, Wang Y, Qian B, Hariharan G, McGeachy S: Mapping of putative virulence motifs of infectious salmon anemia virus surface glycoprotein genes. J Gen Virol. 2007, 88: 3100-3111. 10.1099/vir.0.83097-0.

  129. 129.

    Davison AJ, Eberle F, Hayward GS, McGeoch DJ, Minson AC, Pellett PE, Roizman B, Studdert MJ, Thiry E: Family Herpesviridae. Virus Taxonomy. 8th Report ICTV. Edited by: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. 2005, Elsevier Academic Press, San Diego, CA, 193-212.

  130. 130.

    McGeoch DJ, Rixon FJ, Davison AJ: Topics in herpesvirus genomics and evolution. Virus Res. 2006, 117 (1): 90-104. 10.1016/j.virusres.2006.01.002.

  131. 131.

    Waltzek TB, Kelley GO, Alfaro ME, Kurobe T, Davison AJ, Hedrick RP: Phylogenetic relationships in the family Alloherpesviridae. Dis Aquat Organ. 2009, 84: 179-194.

  132. 132.

    Arzul I, Nicolas J-L, Davidson AJ, Renault T: French scallops: a new host for ostreid herpesvirus-1. Virology. 2001, 290: 342-349. 10.1006/viro.2001.1186.

  133. 133.

    Arzul I, Renault T, Lipart C, Davidson AJ: Evidence for interspecies transmission of oyster herpesvirus in marine bivalves. J Gen Virol. 2001, 82: 865-870.

  134. 134.

    Wolf K, Snieszko SF, Dunbar DE, Pyle E: Virus nature of infectious pancreatic necrosis in trout. Proc Soc Exp Med Biol. 1960, 104: 105-108.

  135. 135.

    Delmas B, Kibenge FSB, Leon JC, Mundt E, Vakaharia VN, Wu JL: Family Birnaviridae. Virus Taxonomy. 8th Report ICTV. Edited by: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. 2005, Elsevier Academic Press, San Diego, CA, 561-569.

  136. 136.

    Reno PW: Infectious pancreatic necrosis and associated aquatic birnaviruses. Edited by: Woo PTK, Bruno DW. 1999, CABI Publishing, New York, 1-55. In Fish Diseases and Disorders vol 3

  137. 137.

    Hill BJ, Way K: Serological classification of infectious pancreatic necrosis virus strains determined (IPN) virus and other aquatic birnaviruses. Annu Rev Fish Dis. 1995, 5: 55-57.

  138. 138.

    Blake S, Ma J-Y, Caporale DA, Jairath S, Nicholson BL: Phylogenetic relationships of aquatic birnaviruses based on deduced aminoacid sequences of genome segment A cDNA. Dis Aquat Organ. 2001, 45: 89-102.

  139. 139.

    Cutrín JM, Barja JL, Nicholson BL, Bandín I, Blake S, Dopazo CP: Restriction fragment length polymorphism and sequence analysis: an approach for genotyping infectious pancreatic necrosis virus reference strains and other aquabirnaviruses isolated from Northwestern Spain. Appl Environm Microbiol. 2004, 70: 1059-1067. 10.1128/AEM.70.2.1059-1067.2004.

  140. 140.

    Nishizawa T, Kinoshita S, Yoshimizu M: An approach for genogrouping of Japanese isolates of aquabirnaviruses in a new genogroup, VII, based on the VP2/NS junction region. J Gen Virol. 2005, 86: 1973-1978. 10.1099/vir.0.80438-0.

  141. 141.

    Sorimachi M, Hara T: Characteristic and pathogenicity of a virus isolated form yellowtail fingerlings showing ascetic. Fish Pathol. 1985, 19: 231-238. 10.3147/jsfp.19.231. (in Japanese)

  142. 142.

    Hosono N, Suxuki S, Kusuda R: Evidence for relatedness of Japanese isolates of birnavirus form marine fish to IPNV. J Fish Dis. 1994, 17: 433-347. 10.1111/j.1365-2761.1994.tb00239.x.

  143. 143.

    Romero-Brey I, Bandin I, Cutrín JM, Vakharia VN, Dopazo CP: Genetic analysis of aquabirnaviruses isolated from wild fish reveals occurrence of natural reassortment of infectious pancreatic necrosis virus. J Fish Dis. 2009, 32: 585-595. 10.1111/j.1365-2761.2009.01020.x.

  144. 144.

    Romero-Brey I, Bandin I, Dopazo CP, Barja JL: Isolation of marine birnavirus from new species of wild fishes. Am Fish Soc Fish Health Sec Newslet. 2003, 31: 21-23.

  145. 145.

    Cutrín JM, Lago M, Bandín I, Areoso E, Dopazo CP: Phylogenetic analysis of infectious pancreatic necrosis virus (IPNV) isolated from wild fish in the Galician coastal waters (NW Spain). 8th Int Symp. 2010, Viruses of Lower Vertebrates, Santiago de Compostela, Spain, 25-

  146. 146.

    Chi SC, Lee KW, Hwang SJ: Investigation of host range of fish nodavirus in Taiwan. 10th Int Conf Eur Ass of Fish Pathol, Dublin (Ireland). 2001, Abstract 0-49

  147. 147.

    Chi SC, Shieh JR, Lin SJ: Genetic and antigenic analysis of betanodaviruses isolated from aquatic organisms in Taiwan. Dis Aquat Organ. 2003, 55: 221-228.

  148. 148.

    Mori K, Nakai T, Muroga K, Arimoto M, Mushiake K, Furusawa I: Properties of a new virus belonging to nodaviridae found in larval striped jack (Pseudocaranx dentex) with nervous necrosis. Virology. 1992, 187: 368-371. 10.1016/0042-6822(92)90329-N.

  149. 149.

    Muroga K: Viral and bacterial diseases in larval and juvenile marine fish and shellfish, a review. Fish Pathol. 1995, 30: 71-85. 10.3147/jsfp.30.71.

  150. 150.

    Awang AB: Sea bass (Lates calcarifer) larvae and fry production in Malaysia. Diseases of barramundi (Lates calcarifer) in Australia, a review. Management of Wild and Cultured Sea Bass/Barramundi Lates calcarifer, ACIAR, Canberra. Edited by: Copland JW, Grey DI. 1987, Queensland, Australia, 144-147.

  151. 151.

    Azad IS, Shekhar MS, Thirunavukkarasu AR, Poornima M, Kailasam M, Rajan JJS, Ali SA, Abraham M, Ravichandran P: Nodavirus infection causes mortalities in hatchery produced larvae of Lates calcarifer, first report from India. Dis Aquat Organ. 2005, 63: 113-118.

  152. 152.

    Chang SF, Ngoh GH, Kueh S: Detection of viral nervous necrosis nodavirus by reverse transcription polymerase chain reaction in locally farmed marine food fish. Singapore Vet J. 1997, 21: 39-44.

  153. 153.

    Glazebrook JS, Campbell RSF: Diseases of barramundi (Lates calcarifer) in Australia, a review. Edited by: Copland JW, Grey DI. 1987, Management of Wild and Cultured Sea Bass/Barramundi Lates calcarifer, ACIAR, Canberra, Queensland, Australia, 204-206.

  154. 154.

    Glazebrook JS, Heasman MP, De Beer SW: Picorna-like viral particles associated with mass mortalities in larval barramundi, Lates calcarifer (Bloch). J Fish Dis. 1990, 13: 245-249. 10.1111/j.1365-2761.1990.tb00780.x.

  155. 155.

    Renault T, Haffner P, Baudin LF, Breuil G, Bonami JR: Mass mortalities in hatchery-reared sea bass (Lates calcarifer) larvae associated with the presence in the brain and retina of virus-like particles. Bull Eur Ass Fish Pathol. 1991, 11: 68-73.

  156. 156.

    Ucko M, Colorni A, Diamant A: Nodavirus infections in israeli mariculture. J Fish Dis. 2004, 27: 459-469. 10.1111/j.1365-2761.2004.00565.x.

  157. 157.

    Zafran , Harada T, Koesharyani I, Yuasa K, Hatai K: Indonesian hatchery reared seabass larvae (Lates calcarifer) associated with viral nervous necrosis (VNN). Ind Fish Res J. 1998, 4: 19-22.

  158. 158.

    Jung SJ, Miyazaki T, Miyata M, Oishi T: Histopathological studies on viral nervous necrosis in a new host Japanese sea bass Lateolabrax japonicus. Bull Fac Bioresour Mie-Univ. 1996, 6: 9-16.

  159. 159.

    Bigarre L, Cabon J, Baud M, Heimann M, Body A, Lieffring F, Castric J: Outbreak of betanodavirus infection in tilapia, Oreochromis niloticus (L.) in freshwater. J Fish Dis. 2009, 32 (8): 667-673. 10.1111/j.1365-2761.2009.01037.x.

  160. 160.

    Gagné N, Johnson SC, Cook-Versloot M, MacKinnon A-M, Olivier G: Molecular detection and characterization of nodavirus in several marine fish species from the Northeastern Atlantic. Dis Aquat Organ. 2004, 62: 181-189.

  161. 161.

    Johnson SC, Sperker SA, Leggiadro CT, Groman DB, Griffiths SG, Ritchie RJ, Cook MD, Cusak RR: Identification and characterization of a piscine neuropathy and nodavirus from juvenile Atlantic cod from the Atlantic coast of North America. J Aquat Anim Health. 2002, 14: 124-133. 10.1577/1548-8667(2002)014<0124:IACOAP>2.0.CO;2.

  162. 162.

    Pantel S, Korsnes K, Bergh O, Vik-Mo F, Pedersen J, Nerland AH: Nodavirus in farmed Atlantic cod Gadus morhua in Norway. Dis Aquat Organ. 2007, 77: 169-173.

  163. 163.

    Starkey WG, Ireland JH, Muir KF, Jenkins ME, Roy WJ, Richards RH, Ferguson HW: Nodavirus infection in Atlantic cod and Dover sole in the UK. Vet Rec. 2001, 149: 179-181. 10.1136/vr.149.6.179.

  164. 164.

    Bellance R, Gallet de Saint-Aurin D: L'encéphalite virale du loup de mer. Caraïbes Medical. 1988, 2: 105-114. (in French)

  165. 165.

    Bovo G, Nishizawa T, Maltese C, Borghesan F, Mutinelli F, Montesi F, De Mas S: Viral encephalopathy and retinopathy of farmed marine fish species in Italy. Virus Res. 1999, 63: 143-146. 10.1016/S0168-1702(99)00068-4.

  166. 166.

    Breuil G, Bonami JR, Pepin JF, Pichot Y: Viral infection (picorna-like virus) associated with mass mortalities in hatchery-reared sea-bass (Dicentrarchus labrax) larvae and juveniles. Aquaculture. 1991, 97: 109-116. 10.1016/0044-8486(91)90258-9.

  167. 167.

    Le Breton A, Grisez L, Sweetman J, Ollevier F: Viral nervous necrosis (VNN) associated with mass mortalities in cage reared sea bass, Dicentrarchus labrax (L.). J Fish Dis. 1997, 20: 145-151. 10.1046/j.1365-2761.1997.00284.x.

  168. 168.

    Skliris GP, Krondiris JV, Sideris DC, Shinn AP, Starkey WG, Richards RH: Phylogenetic and antigenic characterization of new fish nodavirus isolates from Europe and Asia. Virus Res. 2001, 75: 59-67. 10.1016/S0168-1702(01)00225-8.

  169. 169.

    Chi SC, Lo CF, Kou GH, Chang PS, Peng SE, Chen SN: Mass mortalities associated with viral nervous necrosis (VNN) disease in two species of hatchery-reared grouper, Epinephelus fuscogutatus and Epinephelus akaara (Temminck & Schlegel). J Fish Dis. 1997, 20: 185-193. 10.1046/j.1365-2761.1997.00291.x.

  170. 170.

    Mori K, Nakai T, Nagahara M, Muroga K, Mekuchi T, Kanno T: A viral disease in hatchery-reared larvae and juveniles of redspotted grouper. Fish Pathol. 1991, 26: 209-210. 10.3147/jsfp.26.209.

  171. 171.

    Lai YS, Murali S, Chiu HC, Ju HY, Lin YS, Chen SC, Guo IC, Fang K, Chan CY: Propagation of yellow grouper nervous necrosis virus (YGNNV) in a new nodavirus-susceptible cell line from yellow grouper, Epinephelus awoara (Temminck & Schlegel), brain tissue. J Fish Dis. 2001, 24: 299-309. 10.1046/j.1365-2761.2001.00303.x.

  172. 172.

    Maeno Y, de la Peňa LD, Cruz-Lacierda E: Nodavirus infection in hatchery-reared Orange-Spotted Grouper Epinephelus coioides, first record of viral nervous necrosis in the Philippines. Fish Pathol. 2002, 37: 87-89. 10.3147/jsfp.37.87.

  173. 173.

    Danayadol Y, Direkbusarakom S, Supamattaya K: Viral nervous necrosis in brownspotted grouper, Epinephelus malabaricus, cultured in Thailand. Diseases in Asian aquaculture II. Edited by: Shariff M, Arthus JR, Subasunghe RP. 1995, Fish Health section. Asian Fisheries Society, Manila, 227-233.

  174. 174.

    Nakai T, Nguyen HD, Nishizawa T, Muroga K, Arimoto M, Ootsuki K: Occurrence of viral nervous necrosis in kelp grouper and tiger puffer. Fish Pathol. 1994, 29: 211-212. 10.3147/jsfp.29.211.

  175. 175.

    Fukuda Y, Nguyen HD, Furuhasi M, Nakai T: Mass mortality of cultured sevenband grouper, Epinephelus septemfasciatus, associated with viral nervous necrosis. Fish Pathol. 1996, 31: 165-170. 10.3147/jsfp.31.165.

  176. 176.

    Sohn SG, Park MA: Viral diseases of cultured marine fish and shrimp in Korea. Fish Pathol. 1998, 33: 189-192. 10.3147/jsfp.33.189.

  177. 177.

    Chua FHC, Loo JJ, Wee JK: Mass mortality in juvenile greasy grouper, Epinephelus tauvina, associated with vacuolating encephalopathy and retinopathy. Edited by: Shariff M, Arthur JR, Subhasinghe P. 1995, Diseases in Asian Aquaculture II, Fish Health Section. Asian Fisheries Society, Manila, 235-241.

  178. 178.

    Zafran Koesharyani JF, Yuasa K, Harada T, Hatai K: Viral nervous necrosis in humpback grouper Chromileptes altivelis larvae and juveniles. Fish Pathol. 2000, 35: 95-96. 10.3147/jsfp.35.95.

  179. 179.

    Pirarat N, Ponpornpisit A, Traithong T, Nakai T, Lakagori T, Maita M, Endo M: Nodavirus associated with pathological changes in adult spottet coral groupers (Plectropomus maculates) in Thailand with viral nervous necrosis. Res Vet Sci. 2009, 87: 97-101. 10.1016/j.rvsc.2009.01.004.

  180. 180.

    Pirarat N, Katagiri T, Maita M, Nakai T, Endo M: Viral encephalopathy in hatchery-reared juvenile thread-sail filefish (Stephanolepis cirrhifer). Aquaculture. 2009, 288: 349-352. 10.1016/j.aquaculture.2008.12.014.

  181. 181.

    Zorriehzahra MJ, Nakai T, Sharifpour I, Gomes DK, Chi SC, Soltani M, Mohd D, Hj H, Sharif Roani M, Saidi AA: Mortality wild golden mullet (Liza auratus) in Iranian waters of the Caspian Sea, associated with viral nervous necrosis like agent, Iran. J Fish Sci. 2005, 45: 43-58.

  182. 182.

    Yoshikoshi K, Inoue K: Viral nervous necrosis in hatchery-reared larvae and juveniles of japanese parrotfish, Oplegnathus fasciatus (Temminck & Schlegel). J Fish Dis. 1990, 13: 69-77. 10.1111/j.1365-2761.1990.tb00758.x.

  183. 183.

    Nguyen HD, Mekuchi T, Imura K, Nakai T, Nishizawa T, Muroga K: Occurrence of viral nervous necrosis (VNN) in hatchery-reared juvenile Japanese flounder Paralichthys olivaceus. Fish Sci. 1994, 60: 551-554.

  184. 184.

    Grotmol S, Totland GK, Kvellestad A, Fjell K, Olsen AB: Mass mortality of larval and juvenile hatchery-reared halibut (Hippoglossus hippoglossus L.) associated with the presence of virus-like particles in vacuolated lesions in the central nervous system and retina. Bull Eur Ass Fish Pathol. 1995, 15 (5): 176-180.

  185. 185.

    Starkey WG, Ireland JH, Muir KF, Shinn AP, Richards RH, Ferguson HW: Isolation of nodavirus from Scottish farmed halibut, Hippoglossus hippoglossus (L). J Fish Dis. 2000, 23 (6): 418-422. 10.1046/j.1365-2761.2000.00254.x.

  186. 186.

    Hegde A, The HC, Lam TJ, Sin YM: Nodavirus infection in freshwater ornamental fish, guppy, Poecilia reticulata- comparative characterization and pathogenicity studies. Arch Virol. 2003, 148: 575-586. 10.1007/s00705-002-0936-x.

  187. 187.

    Oh MJ, Jung SJ, Kim SR, Rajendran KV, Kim YJ, Choi TJ, Kim HR, Kim JD: A fish nodavirus associated with mass mortality in hatchery-reared red drum, Sciaenops ocellatus. Aquaculture. 2002, 211: 1-7. 10.1016/S0044-8486(01)00877-8.

  188. 188.

    Comps M, Trindade M, Delsert C: Investigation of fish encephalitis viruses (FEV) expression in marine fishes using DIG-labelled probes. Aquaculture. 1996, 143: 113-121. 10.1016/0044-8486(96)01264-1.

  189. 189.

    Pavoletti E, Prearo M, Ghittino M, Ghittino C: Casi di encefaloretinopatia in ombrina (Umbrina cirrosa) con descrizione della sintomatologia clinica e del quadro anatomoistopatologico. Boll Soc It Patol Ittica. 1998, 23: 24-33.

  190. 190.

    Curtis PA, Drawbridge M, Iwamoto T, Nakai T, Hedrick RP, Gendron AP: Nodavirus infection of juvenile white seabass, Atractoscion nobilis, cultured in southern California, first record of viral nervous necrosis (VNN) in North America. J Fish Dis. 2001, 24: 263-271. 10.1046/j.1365-2761.2001.00292.x.

  191. 191.

    Bloch B, Gravningen K, Larsen JL: Encephalomyelitis among turbot associated with a picornavirus-like agent. Dis Aquat Organ. 1991, 10: 65-70.

  192. 192.

    Kim SR, Jung SJ, Kim YJ, Kim JD, Jung TS, Choi TJ, Yoshimizu M, Oh MJ: Phylogenic comparison of Viral Nervous Necrosis (VNN) viruses occurring seed production period. J Korean Fish Soc. 2001, 35: 237-241.

  193. 193.

    Bitchava K, Xylouri E, Fragkiadaki E, Athanassopoulou F, Papanastassopoulou M, Sabatakou O: First incidence of clinical signs of nodavirus infection in sea bream, Sparus auratus L. Israeli J Aquaculture. 2007, 59: 3-9.

  194. 194.

    Comps M, Raymond JC: Virus-like particles in the retina of the sea-bream, Sparus aurata. Bull Eur Ass Fish Pathol. 1996, 16: 161-163.

  195. 195.

    Dalla Valle L, Zanella L, Patarnello P, Paolucci L, Belvedere P, Colombo L: Development of a sensitive diagnostic assay for fish nervous necrosis virus based on RT-PCR plus nested PCR. J Fish Dis. 2000, 23: 321-327. 10.1046/j.1365-2761.2000.00255.x.

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11. Acknowledgements

The authors want to thanks Gael Kurath for her very interesting suggestions that helped to improve the quality of this review.

Author information

Correspondence to Carlos P Dopazo.

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9. Authors' contributions

Both authors carried out the compilation and analysis of references related to the subject, as well as the writing and edition of the manuscript. All authors read and approved the final manuscript.

10. Competing interests

The authors declare that they have no competing interests.

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Bandín, I., Dopazo, C.P. Host range, host specificity and hypothesized host shift events among viruses of lower vertebrates. Vet Res 42, 67 (2011).

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