Phylogenomic signatures of a lineage of vesicular stomatitis Indiana virus circulating during the 2019-2020 epidemic in the United States

Authors: ZARATE, SELENE - AUTONOMOUS UNIVERSITY OF MEXICO CITY; BERTRAM, MIRANDA; RODGERS, CASE - COLORADO STATE UNIVERSITY; REED, KIRSTEN - COLORADO STATE UNIVERSITY; PELZEL-MCCLUSKEY, ANGELA - ANIMAL AND PLANT HEALTH INSPECTION SERVICE (APHIS); GOMEZ-ROMERO, NINNET - UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO; MIRE, CHAD; MAYO, CHRISTIE - COLORADO STATE UNIVERSITY; KOSAKOVSKY POND, SERGEI - TEMPLE UNIVERSITY; VELAZQUEZ SALINAS, LAURO; RODRIGUEZ, LUIS - RETIRED ARS EMPLOYEE

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/15/2024
Publication Date: 11/20/2024
Citation: Zarate, S., Bertram, M.R., Rodgers, C., Reed, K., Pelzel-Mccluskey, A., Gomez-Romero, N., Mire, C.E., Mayo, C., Kosakovsky Pond, S., Velazquez Salinas, L., Rodriguez, L.L. 2024. Phylogenomic signatures of a lineage of vesicular stomatitis Indiana virus circulating during the 2019-2020 epidemic in the United States. Viruses. 16(11). Article 1803. https://doi.org/10.3390/v16111803.
DOI: https://doi.org/10.3390/v16111803

Interpretive Summary: Currently, many of the genetic factors associated the evolution of epidemic vesicular stomatitis virus (VSV) lineages during outbreaks in the US is poor understood. In this study, we described the evolution of the epidemic lineage 2019-2020, responsible for one of the largest outbreaks of vesicular stomatitis in the US. Our study shows a comprehensive genomic analysis, identifying not only specific changes in the genome that were promoting the evolution of this epidemic lineage during its circulation in the US, but also recognizing putative mutations between epidemic and endemic lineages that may be promoting the emergence of VSV into the US. Furthermore, the possible implication of these mutations at functional protein level, was a relevant subject also covered during this study. Based on these results, we will test future hypothesis using our infection clone system, to assess the potential role of these mutations in the virulence of pigs a natural host of this virus.

Technical Abstract: For the first time, we describe phylogenomic signatures of an epidemic lineage of vesicular stomatitis Indiana virus (VSIV). We applied multiple evolutionary analyses to a dataset of full-length genome sequences representing the circulation of an epidemic VSIV lineage in the US between 2019 and 2020. Based on phylogenetic analyses, we predicted the ancestral relationship of this lineage with a specific group of isolates circulating in the endemic zone of Chiapas, Mexico. Subsequently, our findings indicate that the lineage diversified into at least four different subpopulations during its circulation in the US. We identified single nucleotide polymorphisms (SNPs) that differentiate viral subpopulations and assessed their potential relevance using comparative phylogenetic methods, highlighting the preponderance of synonymous mutations during the differentiation of these populations. Purifying selection was the main evolutionary force favoring the conservation of this epidemic phenotype, with P and G genes as the main drivers of the evolution of this lineage. Our analyses identified multiple codon sites under positive selection and the association of these sites with specific functional domains at P, M, G, and L proteins. Based on ancestral reconstruction analyses, we showed the potential relevance of some of the sites identified under positive selection to the adaptation of the epidemic lineage at the population level. Finally, using a representative group of viruses from Colorado, we established a positive correlation between genetic and geographical distances, suggesting that positive selection on specific codon positions might have favored the adaptation of different subpopulations to circulation in specific geographical settings. Collectively, our study reveals the complex dynamics that accompany the evolution of an epidemic lineage of VSIV in nature. Our analytical framework provides a model for conducting future evolutionary analyses. The ultimate goal is to support the implementation of an early warning system for vesicular stomatitis virus in the US, enabling early detection of epidemic precursors from Mexico.