Gene Diversification of an Emerging Pathogen: A Decade of Mutation in a Novel Fish Viral Hemorrhagic Septicemia (VHS) Substrain Since Its First Appearance in the Laurentian Great Lakes

Viral Hemorrhagic Septicemia virus (VHSv) is an RNA rhabdovirus that causes one of the world's most serious fish diseases, infecting >80 species across the Northern Hemisphere. A new, novel, and especially virulent substrain -IVb– first appeared in the Great Lakes about a decade ago, with massive fish kills, rapid spread, and considerable genetic diversification. We analyze temporal and spatial mutational patterns in the novel non-virion (Nv) gene and the glycoprotein (G), phosphoprotein (P), and matrix (M) genes. Results show the Nv-gene evolves the fastest (k=1.2x10^-3substitutions/site/yr), with the G-gene at ~1/10, P- at ~1/15, and M-gene at ~1/16  of the Nv-gene’s rate. Patterns of evolutionary changes coincided among the genes for some solates, but appeared independent in others.  Lakes Erie and Ontario contained the greatest haplotype diversity; their isolates are nearer to the substrain’s origin in the nwAtlantic Ocean. New viral variants appeared profuse following the large 2006 outbreak; diversification may have been in response to fish populations developing resistance. Two  2012  variants, isolated from fish lacking classic VHSv symptoms, are markedly genetically distinctive. These patterns of rapid evolutionary differentiation may allow new viral variants to evade fish host recognition and immune responses, facilitating long-time persistence along with expansion to new geographic areas.