Increased virulence of an epidemic strain of vesicular stomatitis virus is associated with interference of the innate response in pigs

Authors: VELAZQUEZ-SALINAS, LAURO - Oak Ridge Institute For Science And Education (ORISE); Pauszek, Steven; STENFELDT, CAROLINA - University Of Minnesota; O'HEARN, EMILY - Animal And Plant Health Inspection Service (APHIS); PACHECO, JUAN - Former ARS Employee; Borca, Manuel; VERDUGO-RODRIGUEZ, ANTONIO - The National Autonomous University Of Mexico; Arzt, Jonathan; Rodriguez, Luis

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/27/2018
Publication Date: 8/15/2018
Citation: Velazquez-Salinas, L., Pauszek, S.J., Stenfeldt, C., O'Hearn, E.S., Pacheco, J.M., Borca, M.V., Verdugo-Rodriguez, A., Arzt, J., Rodriguez, L.L. 2018. Increased virulence of an epidemic strain of vesicular stomatitis virus is associated with interference of the innate response in pigs. Frontiers in Microbiology. 9:1891. https://doi.org/10.3389/fmicb.2018.01891.
DOI: https://doi.org/10.3389/fmicb.2018.01891

Interpretive Summary: Vesicular Stomatitis Virus (VSV) is an arthropod-borne virus that causes serious vesicular disease resulting in economic losses to the cattle, swine, and horse industries due to decreased animal production and quarantines. In cattle and pigs, the disease is clinically indistinguishable from Foot-and-Mouth Disease (FMD), one of the most devastating exotic diseases in livestock. For decades, outbreak cycles of VS lasting 1-3 years have occurred sporadically in the southwestern United States. Different VSV strains causing each of these outbreak cycles are close genetic relatives of specific viruses circulating in enzootic areas of Mexico, but their means of transmission and introduction to the United States remain unclear. Since 2009 and continuing through 2016, there have been outbreaks in the US caused by a single viral strain (lineage 1.1) that was first detected among many other VSV lineages circulating in southern Mexico in 2006. In this manuscript we showed that the virus causing outbreaks in the US caused more severe disease in pigs than its closest genetic relative that remained in Mexico and that this increased virulence was associated to the ability fo the virus to interfere with pigs immune response. This work might help explain the periodic outbreaks of VSV in the USA and predict the occurrence of future outbreaks.

Technical Abstract: Vesicular stomatitis virus (VSV) causes sporadic outbreaks of vesicular disease in the southwestern US. 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.