Exploring the molecular basis of vesicular stomatitis virus pathogenesis in swine: insights from expression profiling of primary macrophages infected with M51R mutant virus

Authors: Velazquez, Lauro; Medina, Gisselle; VALDEZ, FEDERICO - Oak Ridge Institute For Science And Education (ORISE); COLLINSON, SHANNON - Oak Ridge Institute For Science And Education (ORISE); ZARATE, SELENE - Autonomous National University Of Mexico; Zhu, James; Rodriguez, Luis

Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/25/2023
Publication Date: 6/30/2023
Citation: Velazquez Salinas, L., Medina, G.N., Valdez, F., Collinson, S., Zarate, S., Zhu, J.J., Rodriguez, L.L. 2023. Exploring the molecular basis of vesicular stomatitis virus pathogenesis in swine: insights from expression profiling of primary macrophages infected with M51R mutant virus. Pathogens. 12(7). Article 896. https://doi.org/10.3390/pathogens12070896.
DOI: https://doi.org/10.3390/pathogens12070896

Interpretive Summary: In this study, the main goal of this project was to compare by microarray analysis the gene expression of primary porcine macrophages after infection with the recombinant vesicular stomatitis New Jersey viruses rNJ0612NME6 or rNJ0612NME6-M51R. Overall, our results highlight the potential relevance of multiple pathways associated with the type I interferon response as important drivers of the virulence of VSNJV in pigs. A total of 105 genes were identified as a potential candidate to characterize the immune response of field VSV isolates in macrophages in future projects.

Technical Abstract: Our previous study showed that a recombinant New Jersey strain with a mutation (M51R) in the matrix protein, displayed attenuated phenotypes in vivo and in ex-vivo pig macrophages and pigs. However, the molecular mechanisms underlying this attenuation have not been fully elucidated. In this study, gene expression between primary porcine macrophages infected with the M51R virus (rNJ0612NME6-M51R) or its parental virus (rNJ0612NME6) were compared. Analyses of differentially expressed genes (DEGs) revealed fourteen immune-related pathways that were significantly overrepresented as determined by Reactome pathway analysis. Among them, the immune cytokine signaling pathway was found to be the most significantly affected, followed by eight pathways involved in interferon (IFN)-related responses including activation, signaling, induction, and antiviral mechanisms. A total of 105 genes associated with identified pathways were identified as potential candidates for characterizing the immune response of macrophages to field VSV isolates. Interestingly, among these candidates, we identified multiple genes that may play a role in the control of type I IFN during the immune response to VSV in macrophages. Collectively, the results presented herein represent a framework for future analyses directed to understand the molecular factors associated with the pathogenesis of VSV in livestock.