The pathogenesis of nodular myxomatosis. At the site of inoculation (A) viral replication occurs first in the peripheral epidermal cells and then in cells deeper in the dermis (B). This initially induces only a mild primary inflammation and mainly attracts neutrophils at early times. Resident Major Histocompatibility Complex-2 (MHC-2) positive cells, such as Langerhans cells, are also infected (C) [2, 12, 13]. When these cells migrate to the draining lymph node to present viral epitopes in the T-cell zone, they also traffic live virus and T-lymphocytes become infected with MYXV as well (D). This results in wide spread cell death in the T-cell zone of many lymphoid organs and also enables MYXV to spread in a cell-associated manner when these infected T-lymphocytes migrate through the blood and reticuloendothelial circulation. Once in the blood and lymph, MYXV spreads via infected leukocytes to different organs such as the liver, spleen, other distant lymph nodes, testis and epidermis (E). The MYXV replication in these organs induces a strong polymorphonuclear (PMN) cell-influx and in the skin secondary lesions are formed that contain high viral titers, favoring successful spread by mechanical vectors (F) [2, 12].