The BAGV outbreak in 2010 in Spain is the first documented occasion in which this virus has caused disease and mortality in birds, with a strikingly most severe effect on a game bird species, the red-legged partridge. Recently authors reporting on the parallel outbreak of WNV in horses in the same region made the hot summer and high mosquito abundance responsible for both outbreaks. While several cases of WN fever in horses were notified, no new mortality events among game birds were detected during 2011.
Pathology due to BAGV infection had previously not been described in any species as the presence of neutralizing antibodies against BAGV in persons with acute encephalitis in India, could not link the infection clearly to disease symptoms. However, based on sequence analysis, BAGV has been shown to be synonymous to Israel turkey meningoencephalitis virus (ITV), which causes a disease characterized by nonpurulent meningoencephalitis with lymphocytic perivascular infiltrates and focal myocardial necrosis in turkeys in Israel and South Africa, and is controlled by vaccination with live attenuated vaccines[13–15]. The close genetic relationship between the two viruses may mean that BAGV is similarly pathogenic to at least some bird species.
A local hunting estate in the area of the outbreak that conducts direct transect counts on game birds prior to and after the hunting season, reported reduction of red-legged partridge numbers by 86% and in ring-necked pheasants by 29%. Due to the high mortality in red-legged partridges, only ring-necked pheasants were hunted in winter 2010/2011. Hunting bag data from the same hunting estate, showed a reduction in the female/male ratio with respect to previous years (2.4 females/male as opposed to 4 females/male), suggesting that female pheasants were more affected than males.
The degree to which the impact of BAGV in red-legged partridge populations is higher than in ring-necked pheasants and other birds is evidenced by differences in mortality and in the incidence of concomitant disease observed. In all examined partridges BAGV infection appeared to be the primary cause of death (2/6) or disease (4/6), while two of five pheasants and one of the two wood pigeons had severe advanced lesions of concurrent chronic disease (avian tuberculosis). The reason of the higher reduction in numbers in female pheasants, as opposed to males is unclear. With view to a potential higher impact of BAGV, disease due to ITV has also been reported to be more severe and frequent in female than in male turkeys. However other effects such as higher susceptibility of female pheasants to predation, other diseases, or toxic substances employed in agriculture in the area cannot be ruled out.
Differences in the pathogenicity of BAGV for the three species could partly be explained by the differences observed in the distribution and severity of lesions, distribution of viral antigen, and the severe haemosiderosis in partridges, that was moderate in wood pigeons and absent in pheasants. In partridges, BAGV apparently has a wide tropism, targeting different cell types, but especially capillary endothelial cells. In pheasants, neurotropism appears to be somewhat more important while in pigeons only endothelial cells of splenic capillaries seemed to contain BAGV antigen.
One of the most well studied flaviviruses that is known to cause disease in birds is WNV, of which information is available on pathology in naturally infected humans, horses and birds as well as experimental avian and mouse models[9, 16–18]. WNV is known to vary greatly in its virulence in avian species although the mechanism and reasons are still poorly understood[9, 19, 20]. As an example, both endothelial and neural tropism has been described in native North American avian species after natural WNV infection[21–23]. Also in humans and mouse models WNV has been shown to have a diverse cell tropism, leading to a variety of lesions and clinical manifestations[18, 24].
The severe haemosiderosis in red-legged partridges that is the most striking difference to lesions due to BAGV in ring-necked pheasants has previously been described in birds naturally infected by WNV. Hepatic haemosiderosis is most well known as associated to iron overload in captive wild forest birds but is also frequently associated to haemolytic processes in infectious disease. Haemosiderosis and haemorrhage in relation to WNV has been described previously in the spleen and liver of naturally infected North American passeriformes such as the blue jay (Cyanocitta cristata) and the house sparrow (Passer domesticus) as well as raptors and owls from the North American continent[26–28]. It has also been described in wild turkeys (Meleagris gallopavo), but in an outbreak in farmed chukar partridges (Alectoris chukar) and Impeyan pheasants (Lophophorus impeyanu s), only erythrocytophagocytosis was reported in the spleen, while haemosiderosis was not observed. Also, experimental infection of red-legged partridges with Mediterranean WNV isolates did not lead to a noticeable degree of haemosiderosis (the authors, data not published). With view to WNV-associated haemolysis in other species, a few cases of WNV-associated haemorrhagic fever in humans have been described. A recent study has associated sequence signatures in the envelope protein of human pathogenic flaviviruses with the primary syndrome that they produce (encephalitis or haemorrhagic disease). These authors speculated that the electrostatic charge differences caused by the presence of either glycosilated asparagine (Asn, haemorrhagic viruses) or Aspartic acid (Asp, encephalitic viruses) at position 67 of the domain II of the envelope protein could be responsible for the phenotype and related disease syndrome. It would be of interest to further characterize the outbreak-related virus, in order to study these and other features.
In conclusion, BAGV is more pathogenic for red-legged partridges than for ring-necked pheasants and common wood pigeons, and causes a severe haemolytic process in this species. Further (experimental) studies will be necessary to determine the factors that trigger BAGV susceptibility and pathogenesis of the infection in red-legged partridges.