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Research Project: Predicting and Mitigating Vesicular Stomatitis Virus (VSV) Outbreaks in North America

Location: Foreign Arthropod Borne Animal Disease Research

2022 Annual Report


Objectives
Objective 1: Ascertain the viral ecology and factors mediating the introduction and expansion of VSV in the U.S. Objective 1A. Identify viral genetic determinants mediating emergence of epidemic VSV in the U.S. as well as adaptation to insect and animal hosts. Objective 1B. Characterize epidemiological, biotic and abiotic factors associated with vectorial capacity, emergence, incursion, and expansion of VSV from endemic areas into the U.S. Objective 2. Develop intervention strategies to minimize the impact of VSV disease outbreaks. Objective 2A. Develop model-based early warning systems to predict future incursions of VSV from Mexico to the U.S. Objective 2B. Identify vector transmission control strategies based on our understanding of virus-vector-host interactions.


Approach
Objective 1A:The effect of genetic changes on virulence and transmissibility will be investigated with three approaches: 1) investigating virulence in pigs and vector transmissibility in relevant vectors (e.g., midges and black flies); 2) characterizing genomes of the 2019-2020 VSIV U.S. epidemic strains using comparative genomics to identify genetic differences between epidemic and endemic VSIV in Mexico. 3) if different endemic vs. epidemic lineages are identified, then characterize the virulence of these strains. Objective 1B. We will quantify the occurrence of VS cases across space and time in the endemic region in Mexico. Together these data will enable us to quantify the occurrence of VS cases across space and time in the endemic region. If successful, we expect to identify associations between VS cases and environmental/ecological factors. We will employ the big data model integration (BDMI) approach used previously by our VSV-GC collaborators. Objective 2A: Temporal relationships between VS occurrences and variables representing environmental factors relevant to VS transmission will be evaluated. First, municipality level VS occurrence data from 1981 – 2020 provided by SENASICA will be temporally binned based on incursion years into the U.S.: 1985, 1995, 2004, 2012, or 2019. Next, collated datasets representing environmental, ecological and/or biological factors relevant VS occurrences across Mexico for each year identified from Goal 1B.1 will be synchronized with the SENASICA dataset. Initially, time-series analysis of VS occurrence within temporal bins across geographic space will be performed. This analysis will help determine whether VS occurrence and spread outside of the endemic region occurs randomly or non-randomly in space and time prior to incursion in the U.S. We will then test whether identified factors reliably predict incursions to the U.S. using multivariate analyses and, if appropriate, machine learning as previously described. Analyses may reveal genomic markers of virulence to inform surveillance in Mexico and early warning programs. If successful, we expect to identify a reliable set of environmental/ecological/biological variables that can be used to inform early warning metrics in predictive modeling of VSV incursion. Objective 2B: We hypothesize that VSV infection will alter photosensory perception, altering the effectiveness of current phototaxis-dependent surveillance traps and management strategies. If successful, we will determine the effects of VSV infection on midge photoattraction behavior and on the expression of vision or other neurosensory genes.


Progress Report
Despite significant disruption due to COVID-19 restrictions, the Vesicular Stomatitis Virus (VSV) teams in New York and Kansas were able to make substantial progress on all milestones of the newly approved project. Under Objective 1, under a collaborative agreement established in 2021 with Colorado State University, over 400 strains of VSIV from the 2019 outbreak were fully sequenced. The sequences are in the process of being analyzed for phylogeographic analysis. Another important accomplishment was the successful derivation of an infectious Vesicular Stomatitis New Jersey Virus (VSNJV) lineage 1.1 containing the 5 most significant amino acid mutations found in endemic lineage 1.2. This virus is in the process of being characterized both in vitro and in-vivo, we will report the findings in FY23. Though a NACA with New Mexico State University, we were able to travel to Chiapas, Mexico to meet with our collaborators in SENASICA (the Mexican counterpart to USDA). We planned and launched a study to elucidate the spatiotemporal dynamics of different VSV vectors (black flies, sand flies, midges, and mosquitoes) on five farms in the State of Chiapas, an endemic that regularly (almost annually) report cases of VSV. We coupled this with regular reporting of any VSV cases on each farm, and with collection of sera on each farm from cattle over a broad range of ages. Insect vectors are being screened by real-time Rt-PCT for VSV at the SENASICA lab facility in Chiapas. Positive pools of insects and sera from over 150 farm animals were shipped to the USDA-Plum Island Animal Disease Center for virus and antibody assays. In addition, we have acquired from our collaborators at SENASICA a long-term dataset on all reported VSV cases over the last thirty years and, using this data, along with remotely sensed data on climate, land cover/land use, and distribution of domestic animals will determine key variables that predict the distribution of VSV within its endemic range. This study is nearing completion and manuscript preparation is in progress.


Accomplishments


Review Publications
Velazquez-Salinas, L., Pauszek, S.J., Holinka, L.G., Gladue, D.P., Rekant, S.I., Bishop, E.A., Stenfeldt, C., Verdugo-Rodriguez, A., Borca, M.V., Rodriguez, L.L., Arzt, J. 2020. A single amino acid substitution in the matrix protein (M51R) of Vesicular Stomatitis New Jersey virus impairs replication in cultured porcine macrophages and results in significant attenuation in pigs. Frontiers in Microbiology. https://doi.org/10.3389/fmicb.2020.01123.
Palinski, R.M., Pauszek, S., Burruss, D.N., Savory, H., Humphreys, J., Pelzel-McCluskey, A.M., Arzt, J., Peters, D., Rodriguez, L.L. 2020. Whole-genome sequences of Vesicular Stomatitis Virus isolates from the 2004-2006 U.S. outbreaks reveal evidence of molecular adaptation to ecological variables. Molecular Ecology. https://doi.org/10.3390/proceedings2020050076.
Rozo-Lopez, P., Pauszek, S.J., Velazquez Salinas, L., Rodriguez, L.L., Park, Y., Drolet, B.S. 2022. Comparison of endemic and epidemic vesicular stomatitis virus lineages in Culicoides sonorensis midges. Viruses. 14(6):1221-1233. https://doi.org/10.3390/v14061221.