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ARS Home » Plains Area » Manhattan, Kansas » Center for Grain and Animal Health Research » ABADRU » Research » Research Project #433567

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

Location: Arthropod-borne Animal Diseases Research

2020 Annual Report

1. Ascertain the viral ecology of disease and factors mediating the emergence of VSV. 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.

1. A comprehensive analysis of Vesicular Stomatitis (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. Additional data such as water quality monitoring and U.S. census data for human population distribution may be included. 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 in Northern Mexico and the U.S. 3. To identify intervention strategies agains VSV outbreaks, we will first assess the success of specific lineages to spread over a large geographic range and determine the factors of viral virulence not found in strains remaining within endemic foci. This analysis will be conducted through comparison of the pathogeneis of lineage, identification of phyenotypic differences among strains and mutation of infectious genetic clone derived from virulent strain lineage observed in swine. The endemic and epidemic lineages will be compared to determine transmissibility by insect vectors.

Progress Report
This research project is conducted by researchers in both Manhattan, Kansas, and at Plum Island, New York. Objective 1 is to better understand the viral ecology of vesicular stomatitis virus (VSV) disease and the factors that affect its sporadic emergence into the U.S. from Mexico. ARS researchers in Manhattan are contributing to Sub-Objective 1.1 under this objective. For additional progress reports, please refer to project 8064-32000-058-00D. Sub-Objective 1.1: Significant progress was made toward understanding ecological, biological, and physical factors associated with VSV occurrence in the U.S. Several new predictive models were made to examine the complex VSV transmission cycle by black flies, biting midges, and sand flies. The breeding habitats of each of these insect species is different and range from flowing streams to standing water to dry land. Therefore, areas at high risk for VSV can be identified and surveyed for insects based on their proximity to these specific habitats. Changing weather (droughts or intense rains) will alter the abundance of insects and therefore the transmission dynamics. This information helps livestock producers understand the risk of VSV transmission on their property and how to initiate management methods to decrease this risk prior to an outbreak. Objective 2: Progress was made toward developing intervention strategies to minimize the impact of VSV disease outbreaks. This includes developing means to detect and characterize emergent VSV strains, using data to generate models that predict future outbreaks, and identifying transmission control strategies based on our understanding of vector-host interactions. ARS researchers in Manhattan are contributing to three sub-Objectives under this objective. Sub-Objective 2.1: Significant progress was made toward understanding the insect-host interactions of VSV in Culicoides biting midges. In the southwestern U.S., VSV has sporadic patterns of occurrence. The viral lineages causing U.S. outbreaks are closely related to viruses maintained in endemic areas of central and southern Mexico. ARS researchers are evaluating how genetic differences between viruses that get out of Mexico, compared to those that don’t, affect their ability to infect and be transmitted by Culicoides biting midges. Infectious virus lineages representing one strain that emerged from Mexico (lineage 1.1) and one that did not (lineage 1.2) were synthesized by ARS researchers in New York and shipped to ARS Kansas. To examine virus growth in cells, studies were conducted in pig and insect cell cultures. To look at how these viruses grew in midges, infections were initiated by injecting midges intrathoracically and then sampling them over time. Preliminary results show the two genetic lineages grow similarly in both cells and insects. Additionally, there were no differences in midge survival rates nor egg laying rates between the lineages. Information on each particular viral strain's efficiency to replicate and disseminate in the midge will inform potential emergence and transmission risk of similar strains in the U.S. Blood feeding is a critical component of VSV transmission by insects. Fevers in horses, cattle and swine often correlate to high amounts of virus in the blood. ARS researchers are investigating whether midges have a blood meal temperature preference and if this preference changes when insects are infected with VSV. Preliminary results show an increased preference for higher bloodmeal temperatures for the midge’s first meal. This suggests midges may target infected, feverish animals for bloodmeals. This is an advantage to the virus as it increases the likelihood of being picked up by the insect. Results also showed an increased preference for lower temperature bloodmeals on subsequent feedings, suggesting that infected midges may then target healthy, non-febrile animals. Again, this is an advantage to the virus as it increases the likelihood of virus being transmitted to healthy animals. These results will inform transmission dynamics and overall VSV epidemiology, critical for outbreak control strategies. Culicoides biting midges have significant disruptive effects on agriculture as both pests and as virus transmission vectors. Environmental temperature mediates the metabolic rate in midges and causes alterations in oviposition, survival, and arboviral replication. Research is in progress to understand the effects of environmental temperature on VSV infection, dissemination, and transmission. Preliminary results showed that midges held at temperatures from 20 to 30 degrees Celsius sustained high amounts of virus, suggesting high transmission potential at all temperatures. However, low (20°C) and high (30°C) environmental temperatures significantly affected midge survival rates and shift biting-oviposition cycles by 1 to 2 days. These results confirm that environmental temperatures have direct implications on midge behavior and therefore VSV transmission rates and epidemiology. Results will inform VSV predictive modelling development for changing global climatic conditions. Culicoides midges play an essential role in VSV outbreaks. Therefore, the biology of these insects impacts VSV epidemiology. Preliminary results show midge infection rates are affected by multiple bloodmeals, multiple gonotrophic cycles, the age of the midge at the time of infection, and the infectious dose ingested during the initial blood feeding. We found that (1) multiple, non-infectious blood meals significantly increase the virus titers; (2) older midges sustain higher virus titers than younger midges; and (3) the minimum infectious dose for midges is 10,000 fewer virus particles than expected. These findings emphasize the importance of feeding behaviors for estimating VSV transmission risk. Results will inform VSV predictive modelling and insect-targeted control strategies to prevent future outbreaks. Sub-Objective 2.2: Progress was made toward developing models to predict the emergence and spread of VSV in the U.S. using information obtained from the studies above, with the goal of determining correlations between biological and physical factors that favor abundant insect vector populations in the vicinity of susceptible livestock models that describe connected networks for emergence and spread of VSV infection of the vectors are in development. As part of the VSV Grand Challenge group, several new models including the “hot spot” analysis (identification of high-risk areas) helped identify areas for increased insect surveillance. The Animal and Plant Health Inspection Service partnered with ARS to conduct increased surveillance in Western Kansas based on these analyses. The objective was to determine how accurate the models were and measure which insect vector species were present and how many of each. Field trapping is ongoing and will help farmers determine when to initiate control or management measures based on weather patterns and prior to disease detection. Sub-Objective 2.3: Progress was made toward identifying strategies to control transmission of VSV based on our understanding of vector-host interactions. The goal is to create a customizable integrated pest management plan for small farms based on insect and animal behaviors. A new biting insect mitigation system was designed based on cattle and horse farmer stakeholder feedback. Management methods are typically very limited on dairies due to residual pesticides and horse owners are typically reluctant to apply chemicals to their animals. Therefore, a novel spatial repellent system has been designed that protects an area for the animals during moderate to high insect biting times. The new system is solar powered and uses fans to disperse repellent. Each system is fully autonomous, portable, and can be located or relocated to any area within a pasture. This is an important new tool for controlling biting insect helping farmers protect their livestock and companion animals without overexposing them to chemicals.

1. Culicoides biting midges can transmit vesicular stomatitis virus between males and females during mating. Biting midges are well-known agricultural pests and are able to transmit vesicular stomatitis virus (VSV) to cattle, horses, and swine. VSV outbreaks occur every 3-8 years in the U.S. and result in significant economic losses due to animal health, animal movement restrictions, and quarantines. In temperate regions, viruses can overwinter in the absence of infected animals through unknown mechanisms, to reoccur the next year. To better understand whether virus may be maintained in insect populations to result in these multi-year outbreaks, we examined whether virus could pass between male and female midges during mating. ARS researchers showed that VSV-infected females could transmit virus to uninfected naïve males, and infected males could transmit virus to uninfected naïve females. Using staining techniques, examining dissected reproductive organs, and observing midge mating behavior, we were able to determine relevant anatomical sites for virus location and to hypothesize the potential mechanism for venereal VSV transmission in midges during copulation. This research shows the importance of males in VSV transmission dynamics, and the role vectors may play in the maintenance of VSV. This is the first evidence for venereal transmission of any arbovirus in Culicoides spp. biting midges, and the first evidence for venereal transmission of VSV in any known vector species. These results highlight the need to incorporate alternative routes of transmission in understanding arbovirus outbreaks, and could lead to a more comprehensive understanding of: 1) potential virus persistence in nature during between outbreaks; 2) the ability of some virus strains to survive through the winter leading to multi-year outbreaks; and 3) virus transmission dynamics during outbreaks.

2. Evaluating the return on investment of money spent during disease outbreaks. Viruses will continue to emerge and generate an increased public and veterinary health burden around the globe. Significant resources (money, personnel, and time) are redirected during viral outbreaks to intensively study the emergent problem. However, the longer-term results, or return on investment (ROI), of viral outbreak stimulus funding is not as well understood or quantified. This study provided a longitudinal perspective on how the emergence of insect-borne viruses in North America triggered reactionary funding by sponsored agencies, stimulating a significant increase in peer-reviewed publications, innovative development of insect traps, vaccines or other novel mitigation/surveillance tools, and augmented local capacity and skills. Therefore, the ROI of focused outbreak research is immediate, but the new methods, knowledge, and skills will persist longer providing sustained impact on future outbreaks.

Review Publications
Rozo-Lopez, P., Londono-Renteria, B., Drolet, B.S. 2020. Venereal transmission of vesicular stomatitis virus by Culicoides sonorensis midges. Pathogens. 9(4):316.