Phenotypical differences between the epidemic strains of VSV serotype Indiana 98COE and IN0919WYB2 using an in-vivo pig (Sus scrofa) model

Authors: HOLE, KATE - Canadian Food Inspection Agency-National Centre For Foreign Animal Disease; SROGA, PATRYCJA - Canadian Food Inspection Agency-National Centre For Foreign Animal Disease; NEBROSKI, MICHELE - Canadian Food Inspection Agency-National Centre For Foreign Animal Disease; HANDEL, KATHY - Canadian Food Inspection Agency-National Centre For Foreign Animal Disease; LUNG, OLIVER - Canadian Food Inspection Agency-National Centre For Foreign Animal Disease; Spinard Iii, Edward; ZARATE, SELENE - Autonomous University Of Mexico City; NFON, CHARLES - Canadian Food Inspection Agency-National Centre For Foreign Animal Disease; Mire, Chad; Velazquez Salinas, Lauro; BABIUK, SHAWN - Canadian Food Inspection Agency-National Centre For Foreign Animal Disease; RODRIGUEZ, LUIS - Retired ARS Employee

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2024
Publication Date: 12/13/2024
Citation: Hole, K., Sroga, P., Nebroski, M., Handel, K., Lung, O., Spinard Iii, E.J., Zarate, S., Nfon, C., Mire, C.E., Velazquez Salinas, L., Babiuk, S., Rodriguez, L. 2024. Phenotypical differences between the epidemic strains of VSV serotype Indiana 98COE and IN0919WYB2 using an in-vivo pig (Sus scrofa) model. Viruses. 16(12). Article 1915. https://doi.org/10.3390/v16121915.
DOI: https://doi.org/10.3390/v16121915

Interpretive Summary: Currently, many of the biological factors associated the presentation of epidemic outbreaks in the US is poorly understood. In this study, we identified that the ability of vesicular stomatitis virus (VSV) to be transmitted by direct contact among natural hosts, represent a disparate characteristic among epidemic lineages of VSV. This characteristic was correlated with the differences at epidemiological level produced by two distinct epidemic lineages related to the outbreaks in the US during 1997-1998 and 2019-2020. The results of this study represent the framework for future research to identify the genetic basis associated with the transmissibility among VSV strains.

Technical Abstract: During the past 25 years, vesicular stomatitis virus (VSV) has produced multiple epidemic outbreaks in the US, resulting in the emergence of different viral lineages. Currently, very little is known about the pathogenesis of many of these lineages, thus limiting our understanding of the potential biological factors favoring each lineage in these outbreaks. The aim of this study was to determine the potential phenotypical differences between two epidemic strains of the VSV Indiana serotype using a pig model. These strains are representative of the epidemic lineages that affected the US between 1997-1998 (IN98COE) and 2019-2020 (IN0919WYB2), the latter being the last lineage responsible for one of the most extensive outbreaks in the US. Our initial genome analysis revealed the existence of 121 distinct mutations between both strains, including the presence of a 14-nucleotide insertion in the intergenic region between G and L genes observed in IN0919WYB2. The levels of viral RNA in clinical samples between pigs infected with IN98COE or IN0919WYB2 were compared. Overall higher and prolonged expression of viral RNA in pigs infected with IN98COE was observed. However, IN0919WYB2 was slightly more virulent than its IN98COE as it had the ability to produce infection through contact transmission. A higher number of samples from pigs infected with IN0919WYB2 had infectious virus as revealed by virus isolation in cell culture, implying that it may shed virus at higher levels during infection. Sequence analyses conducted from isolates recovered from both experimental groups revealed that IN0919WYB2 was able to induce an increased number of viral variants during the infection, denoting the potential of this strain to rapidly evolve after a single infection-contact transmission event in pigs. Collectively, the results showed that epidemic strains of VSV may represent disparate phenotypes for livestock, a situation that may impact the intensity of an epidemic outbreak. They also highlight the importance of redefining the concept of virulence in VSV beyond the ability of viral strains to induce vesicular lesions during the infection in livestock.