Vesicular stomatitis virus (VSV) causes sporadic outbreaks of vesicular disease in the southwestern United States. The intrinsic characteristics of epidemic strains associated with these outbreaks are poorly understood. In this study, we report the distinctive genomic and biological characteristics of an epidemic (NJ0612NME6) strain of VSV compared with an endemic (NJ0806VCB) strain. Genomic comparisons between the two strains revealed a total of 111 nucleotide differences (23 non-synonymous) with potentially relevant replacements located in the P, G, and L proteins. When tested in experimentally infected pigs, a natural host of VSV, the epidemic strain caused higher fever and an increased number of vesicular lesions compared to pigs infected with the endemic strain. Pigs infected with the epidemic strain showed decreased systemic antiviral activity (type I - IFN), lower antibody levels, higher levels of interleukin 6, and lower levels of tumor necrosis factor during the acute phase of disease compared to pigs infected with the endemic strain. Furthermore, we document the existence of an RNAemia phase in pigs experimentally infected with VSV and explored the cause for the lack of recovery of infectious virus from blood. Finally, the epidemic strain was shown to be more efficient in down-regulating transcription of IRF-7 in primary porcine macrophages. Collectively, the data shows that the epidemic strain of VSV we tested has an enhanced ability to modulate the innate immune response of the vertebrate host. Further studies are needed to examine other epidemic strains and what contributions a phenotype of increased virulence might have on the transmission of VSV during epizootics.
Keywords: IL-6; TNF; epidemics; immune response; interferon; parthenogenesis; vesicular stomatitis; virulence.