Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae

Mona C. Gjessing, Natalya Yutin, Torstein Tengs, Tania Senkevich, Eugene Koonin, Hans Petter Rønning, Marta Alarcon, Sonja Ylving, Kai-Inge Lie, Britt Saure, Linh Tran, Bernard Moss, Ole Bendik Dale

Poxviruses are large DNA viruses of vertebrates and insects causing disease in many animal species including reptiles, birds and mammals. Although poxvirus-like particles were detected in diseased farmed koi carp, ayu and Atlantic salmon, their genetic relationships to poxviruses were not established. Here, we provide the first genome sequence of a fish poxvirus, which was isolated from farmed Atlantic salmon, and use qPCR and immunohistochemistry to describe aspects of salmon gill poxvirus disease. The gill was the main target organ where immature and mature poxvirus particles were detected in detaching, apoptotic respiratory epithelial cells, preceding clinical disease in the form of lethargy, respiratory distress and mortality. In moribund salmon blocking of gas exchange would likely be caused by adherence of respiratory lamellae and epithelial proliferation obstructing respiratory surfaces. The virus was not found in healthy salmon or in controls of gill disease without apoptotic cells, although transmission remains to be demonstrated. PCR on archival tissue confirmed virus infection in 14 cases with gill apoptosis in Norway starting from 1995. Phylogenomic analyses showed that the fish poxvirus is the deepest available branch of chordopoxviruses. The virus encompasses most key chordopoxvirus genes that are required for genome replication and expression although the gene order is substantially different. Nevertheless, many highly conserved chordopoxvirus genes involved in viral membranes biogenesis or virus-host interactions are missing. Instead, the salmon poxvirus carries numerous genes encoding unknown proteins many of which have low sequence complexity and contain simple repeats suggestive of intrinsic disorder or distinct protein structures. Aquaculture is an increasingly important global source of high quality food. To sustain this growth, disease control in fish farming is essential. Moreover, the spread of disease from farmed fish to wild life is a concern. Serious poxviral diseases are emerging in aquaculture, but very little is known about the viruses and the diseases they cause. There is a possibility that viruses may spread to new species with enhanced virulence as has occurred with the myxoma poxvirus in rabbits. Provision of the first fish poxvirus genome sequence and specific diagnostics for the salmon gill poxvirus in Atlantic salmon may help curb this disease and provide comparative knowledge. Furthermore, because salmon gill poxvirus represents the deepest branch of chordopoxvirus so far discovered, the genome analysis provided substantial insight into the evolution of different functional modules in this important group of viruses.