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Research Project: Ecology of Vesicular Stomatitis Virus (VSV) in North America

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2021 Annual Report


Objectives
1. Ascertain the viral ecology of disease and factors mediating the emergence of VSV, including the characterizing epidemiological factors associated with the maintenance of disease in endemic versus non-endemic settings (ABADRU) and (FADRU), determining the environmental conditions that influence vector dominance in endemic versus non-endemic settings, and identifying environmental-vector interactions responsible for the emergence of viral infections in new geographical locations. 1.A. Characterize epidemiological, biotic and abiotic factors associated with the emergence and transmission of VSV in endemic versus non-endemic settings. 2. Develop intervention strategies to minimize the impact of VSV disease outbreaks. 2.A. Develop means to detect and characterize emergent VSV strains and use these data to generate models that predict future outbreaks. 2.B. Identify vector transmission control strategies based on our understanding of vector-host interactions. 3. Ascertain the viral ecology of disease and factors mediating the emergence of VSV, including factors associated with the maintenance of disease, determining the environmental conditions that influence vector dominance in endemic versus non-endemic settings, and identifying environmental-vector interactions responsible for the emergence of viral infections in new geographical locations. 4. Establish research program on Crimean Congo Hemorrhagic Fever (CCHF) and Nipah Virus Disease (NiVD), including development of detection and diagnostic in vectors and hosts as well as studying mechanisms of inter-species transmission.


Approach
1. A comprehensive analysis of VS outbreaks occurring in the U.S. from 2004-2016 will be conducted to determine the relationship between the geographical location of premises reporting VS outbreaks and the spatial and temporal variability in a large suit of ecological variables. Multiple data streams involving disease occurrence and ecological conditions will be obtained from multiple sources and harmonized for integration and analysis. These data sources include; a) outbreak occurrence data inclusive of geo-location, host species, number of animals affected and onset date, b) ecological data analysis c) biotic and abiotic variables inclusive of animal density, hydrological features and streams, elevation and surface water properties, air temperature and precipitation, vegetation ENSO (El Nino Southern Oscilation) data, soil properties and long term trends in environmental variables. . These data will be harmonized and univariate and multivariate statistical analysis will be conducted to determine the best set of explanatory variables for temporal and spatial patterns. These analyses will be used to identify ecological variables associated with VS disease occupancy and spread in the western U.S. and to develop predictive models for disease spread. 2. The characterization of VSV transmission in endemic vs non-endemic settings will be conducted in collaboration with Mexico’s SENASICA-EADC laboratory to conduct genomic sequencing and phylogeographic characterization of viral strains collected through VS surveillance activities in Mexico and to identify the ecological and environmental factors associated with the occurrence of VSV in Mexico. A collaboration with USDA-APHIS will established to determine the phylogeopraphic characteristics of VSV strains causing outbreaks in the U.S. This information will be used to create predictive models for VSV occurrence. 3. A comprehensive analysis of VS outbreaks occurring in the U.S. will be conducted to determine the relationship between geographical location of premises reporting VS outbreaks and spatial and temporal variability in a large suit of ecological variables. Ecology studies in the sw US will be expanded to include endemic areas in Mexico and environmental-vector interactions responsible for the emergence of viral infections in new geographical locations. These data will be harmonized and statistical analysis will be conducted to determine the best set of explanatory variables for temporal and spatial patterns. These analyses will be used to identify ecological variables associated with VS disease emergence, re-emergence and spread in the western U.S. and to develop predictive models for disease spread. 4. A new research program will be started at the Centers for Disease Control and Prevention on CCHF and NiVD. Research scientists will be embedded within existing research programs to develop expertise working in biosafety level 4 facility, develop necessary reagents and methodologies for studying virus host interaction in livestock species. Initial work will focus on molecular detection tools, reverse genetics systems, immunological reagents for studies in small animal models.


Progress Report
Despite multiple setbacks this year associated with personnel constraints and negative impacts of COVID-19, progress was made on this research project. In the previous FY, a manuscript was published in Ecosphere describing a predictive biology approach to Vesicular Stomatitis (VS) in North America, based on 2004-2006 and 2012-2015 VS outbreaks. In FY21 a second manuscript was submitted and accepted in Ecosphere entitled “Evolution and Expansion Dynamics of a Vector-borne Virus: 2004-2006 U.S. Vesicular Stomatitis Outbreak in the Western U.S.” This manuscript based on next-generation sequencing of full-length genomes, showed, rather than a simple geographic relationship, Vesicular Stomatitis Virus (VSV) viral genetic groups are associated with seasonally varying environmental variables such as evaporative demand, soil moisture, and precipitation. This suggests a functional role for these environmental factors in shaping the evolution and ecology of vesicular stomatitis. A nexus to insect-vector switching and possible adaptation to local environmental conditions helped explain the observed incursion-expansion dynamic in the U.S. in the 2004-2006 outbreak. The approach of linking the phytogeography of a virus with the ecology of insect vectors can be applied to other vector-borne diseases. In FY21 we continued targeted vector sampling at identified sites associated with VSV cases along the Rio Grande in southern New Mexico. A total of 40,699 black flies were collected between March 26th, 2020, to December 17th, while an outbreak of VS Indiana virus was occurring in southern New Mexico. Five black fly species were identified using morphology and DNA barcoding. Most interestingly, VSIV was detected by real-time PCR and virus isolation and showed to be identical to viruses circulating in horses in farms miles away from the collection site. This represents the first detection of VSV in the western U.S. from vectors that were not collected on-premises with infected domestic animals. A manuscript is being prepared to describe these findings. In Objective 4, a new research program focusing on Crimean-Congo hemorrhagic fever disease ecology and pathogenesis was started at the Centers for Disease Control and Prevention and the University of California Davis One Health Institute. Three postdoctoral research associates were hired and trained at their respective institutes working in Biosafety Level 4 facilities and also establishing ecological studies in endemic regions of Africa. Despite the SARS-Cov2 pandemic, the research project in West and East Africa (Sierra Leone and Tanzania) has been very successful in collecting thousands of ticks and blood samples from livestock (cattle, goats) in areas with a high risk of CCHF. Samples will be shipped to the Center for Disease Control (CDC) for Crimean-Congo Hermorrhagic Fever (CCHF) testing.


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.