Assessing Pathogenicity And Innate Immune Modulatory Activity Of Viral Hemorrhagic Septicemia Virus Upon Matrix Protein Mutation

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Viral Hemorrhagic Septicemia Virus (VHSV) causes a highly contagious, deadly systemic disease to a wide range of fish (>90 species); it is an OIE notifiable disease because it threatens wild and cultured fish world-wide. Novirhabdoviruses (fam. Rhabdoviridae) are enveloped RNA viruses that replicate in the cytoplasm and express 6 viral genes encoding structural and nonstructural proteins, some of which remain poorly characterized. High mortality outbreaks have affected up to 28 fish species in the Great Lakes watershed since 2003, caused by the VHSV-IVb sub-genotype. Our previous studies assessed how VHSV-IVb Matrix protein (M) acts as a potent inhibitor of host transcription. Using a reverse genetic system, single or double amino acid changes to M were incorporated into a recombinant wild type (rWT) VHSV-IVb. Following amplification of M-mutants on BF-2 cells, their pathogenicity and immunogenicity were assessed in vitro upon EPC cells infection. VHSVIVb harboring double mutations showed a reduced anti-transcriptional activity, but also decreased replicative abilities as compared to rWT. VHSV-IVb harboring a single mutation showed a slight decreased anti-transcriptional action, but retained rWT replicative capacity. Interestingly, both mutants allowed elevated antiviral host responses when compared to rWT infection. Currently, sanitary prophylaxis is the only way to contain VHS outbreaks; despite decades of effort, commercial vaccines against VHSV are not yet available or approved for widespread use. Infective viral strains attenuated by reverse genetic could provide a valuable platform towards an attenuated VHSV vaccine, thus our double mutant could be a good candidate.


Presented at the EFHW Conference, Michigan State University.