Genomic and immunogenic changes of Piscine novirhabdovirus (Viral Hemorrhagic Septicemia Virus) over its evolutionary history in the Laurentian Great Lakes

A unique and highly virulent subgenogroup (-IVb) of Piscine novirhabdovirus, also known as Viral Hemorrhagic Septicemia Virus (VHSV), suddenly appeared in the Laurentian Great Lakes, causing large mortality outbreaks in 2005 and 2006, and affecting >32 freshwater fish species. Periods of apparent dormancy have punctuated smaller and more geographically-restricted outbreaks in 2007, 2008, and 2017. In this study, we conduct the largest whole genome sequencing analysis of VHSV-IVb to date, evaluating its evolutionary changes from 48 isolates in relation to immunogenicity in cell culture. Our investigation compares genomic and genetic variation, selection, and rates of sequence changes in VHSV-IVb, in relation to other VHSV genogroups (VHSV-I, VHSV-II, VHSV-III, and VHSV-IVa) and with other Novirhabdoviruses. Results show that the VHSV-IVb isolates we sequenced contain 253 SNPs (2.3% of the total 11,158 nucleotides) across their entire genomes, with 85 (33.6%) of them being non-synonymous. The most substitutions occurred in the non-coding region (NCDS; 4.3%), followed by the Nv- (3.8%), and M- (2.8%) genes. Proportionally more M-gene substitutions encoded amino acid changes (52.9%), followed by the Nv- (50.0%), G- (48.6%), N- (35.7%) and L- (23.1%) genes. Among VHSV genogroups and subgenogroups, VHSV-IVa from the northeastern Pacific Ocean has shown the fastest substitution rate (2.01x10-3), followed by VHSV-IVb (6.64x10-5) and by the VHSV-I, -II and-III genogroups from Europe (4.09x10-5). A 2016 gizzard shad (Dorosoma cepedianum) from Lake Erie possessed the most divergent VHSV-IVb sequence. The in vitro immunogenicity analysis of that sample displayed reduced virulence (as did the other samples from 2016), in comparison to the original VHSV-IVb isolate (which had been traced back to 2003, as an origin date). The 2016 isolates that we tested induced milder impacts on fish host cell innate antiviral responses, suggesting altered phenotypic effects. In conclusion, our overall findings indicate that VHSV-IVb has undergone continued sequence change and a trend to lower virulence over its evolutionary history (2003 through present-day), which may facilitate its long-term persistence in fish host populations.

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Genomic and immunogenic changes over the history of the Viral Hemorrhagic Septicemia (VHS-IVb) fish virus (=Piscine novirhabdovirus) in the Laurentian Great Lakes

10.1101/2020.04.27.063842 ◽

2020 ◽

Author(s):

Megan D. Niner ◽

Carol A. Stepien ◽

Bartolomeo Gorgoglione ◽

Douglas W. Leaman

Keyword(s):

Great Lakes ◽

Fish Host ◽

Laurentian Great Lakes ◽

Viral Hemorrhagic Septicemia Virus ◽

Coding Region ◽

Nucleotide Substitutions ◽

Whole Genome Analysis ◽

Viral Hemorrhagic Septicemia ◽

History Of

AbstractViral Hemorrhagic Septicemia Virus (VHSV) (=Piscine novirhabdovirus) appeared in the Laurentian Great Lakes in 2005, constituting a unique and highly virulent genogroup (IVb), which killed >32 fish species in large 2005 and 2006. Periods of apparent dormancy punctuated smaller outbreaks in 2007, 2008, and 2017. We conducted the first whole genome analysis of IVb, evaluating its evolutionary changes using 46 isolates, in reference to immunogenicity in cell culture, and the genomes of other VHS genogroups (I–IVa) and other Novirhabdoviruses. IVb isolates had 253 genomic nucleotide substitutions (2.3% of the total 11,158 nucleotides), with 85 (16.6%) being non-synonymous. The greatest number of substitutions occurred in the non-coding region (NCDS; 4.3%) followed by the Nv- (3.8%), and M- (2.8%) genes. The M-gene possessed the greatest proportions of amino acid changes (52.9%), followed by the Nv- (50.0%), G- (48.6%), N- (35.7%) and L- (23.1%) genes. Among VHS genogroups, IVa from the northeastern Pacific exhibited the fastest substitution rate (2.01×10-3), followed by Ivb (6.64×10−5), and I/III from Europe (4.09×10−5). A 2016 gizzard shad isolate from Lake Erie was the most divergent IVb isolate (38 NT, 15.0%, 15 AA), yet exhibited reduced virulence with in vitro immunogenicity analyses, as did other 2016 isolates, in comparison to the first IVb isolate (2003). The 2016 isolates exhibited lower impact on innate antiviral responses, suggesting phenotypic effects. Results suggest continued sequence change and lower virulence over the history of IVb, which may facilitate its long-term persistence in fish host populations.

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