Research Project: Rift Valley Fever Pathogenesis and Epidemiology

Location: Foreign Arthropod Borne Animal Disease Research

Project Number: 3022-32000-024-000-D
Project Type: In-House Appropriated

Start Date: Nov 16, 2021
End Date: Nov 15, 2026

Objective:
Objective 1: Identify factors associated with Bunyaviridae (Rift Valley Fever virus) infections, pathogenesis and maintenance in vector and animal hosts. • Characterize host, vector and bunyavirus interactions (molecular and cellular) associated with virus infection. • Characterize the host immune response in susceptible animal hosts and determine influences that determine clinical outcomes during primary RVFV infections. • Further identify competent mosquito species in the United States that can amplify and spread RVFV, and also investigate the capacity for U.S. culicoides and ticks to become competent vectors. • Identify mosquito species that transmit RVFV transovarially. • Determine the risk of transmitting RVFV through unpasteurized milk consumption. • Determine the risk of transmitting RVFV through semen. • Determine the infectious period of RVF virus in cattle and sheep (the period of viremia sufficiently high to result in infection of mosquitoes) and use these data to improve epidemiological models. Sub-objective 1.A: Identify cellular factors important for replication and pathogenesis in the vector and the mammalian host. Sub-objective 1.B: Characterize host immune response and determine influences that effect clinical outcomes during primary RVFV infections in susceptible hosts. Sub-objective 1.C: Competence of North American arthropods to RVFV. Sub-objective 1.D: Identify the ability of mosquitoes to vertically transmit RVFV to the next generation. Sub-objective 1.E: Assessment of risks associate with non-vector routes of RVFV transmission. Objective 2: Identify factors affecting the inter-epidemic cycle and disease emergence caused by Rift Valley Fever virus. • Identify epidemiological and ecological factors affecting the inter-epidemic cycle. • Develop means to detect and characterize emergent arboviral diseases and use these data to generate models that predict future outbreaks. • Determine the infectious period of RVF virus in cattle and sheep (the period of viremia sufficiently high to result in infection of mosquitoes) and use these data to improve epidemiological models. Sub-objective 2.A: Examine the effects of temperature on the extrinsic incubation period of RVFV in various mosquito species. Sub-objective 2.B: Develop deployable tools for rapid diagnostics of RFVF. Sub-objective 2.C: Determination of viremic titers needed for transmission of RVFV to mosquitoes. Objective 3: Develop intervention strategies to effectively control Rift Valley Fever virus and contain disease outbreaks. • Evaluate and improve existing and new diagnostic tests and testing strategies for RVF virus surveillance, detection, and recovery from disease outbreaks. • Evaluate existing vaccine platforms and develop strategies designed to rapidly control and prevent RVF virus outbreaks. Sub-objective 3.A: Evaluation and development of immune-based diagnostic tests for RVFV. Sub-objective 3.B: Develop and evaluate a vaccine platform to control and prevent RVF virus outbreaks.

Approach:
Rift Valley fever (RVF) is a long-recognized disease of domestic livestock in Africa caused by the arthropod-borne virus, Rift Valley Fever virus (RVFV). RVFV is a zoonotic pathogen present on the World Organisation for Animal Health (WOAH) list of notifiable animal diseases of concern and the World Health Organization priority disease list. RVFV is a significant threat to U.S. livestock due to the presence of naïve host populations and competent vectors. RVFV transmission is dependent on complex interactions involving virus, arthropod vector, mammalian host, and environment. Despite the importance of this disease, many elements for RVFV replication, pathogenesis, transmission, and disease epidemiology are poorly understood. To address these gaps, this study has three objectives: 1). Identify factors associated with Rift Valley Fever virus infections, pathogenesis and maintenance in vector and animal hosts, 2) Identify factors affecting the inter-epidemic cycle and disease emergence caused by Rift Valley Fever Virus, and 3) Develop intervention strategies to effectively control Rift Valley Fever virus and contain disease outbreaks. Objectives 1 and 2 will be addressed by examining different aspects of the maintenance and transmission of RVFV. These include examining the roles of North American arthropods as primary and auxiliary vectors in virus transmission, assessing the ability of vertical transmission by mosquitoes, and the stability of RVFV in milk and semen as a non-vector route of transmission. In addition, the effects of temperature on RVFV extrinsic incubation period will be examined. The host response will also be examined as part of objective 1. The importance of GTPases in the regulation of virus replication in the disparate hosts will be examined in a set of studies. An additional study will examine the influence of RVFV Gn and Gc antigens on anti-RVFV neutralizing antibodies in animals with different clinical outcomes. Objectives 2 and 3 will be addressed by examining surveillance and control strategies. For control strategies, existing vaccine platforms will be examined through designing and characterizing a RVFV vaccine vector based on the recombinant Vesicular Stomatitis Virus (rVSV) vaccine platform expressing the Gn and Gc RVFV antigens. As part of the diagnostics and surveillance, both molecular and immunological assays will be developed and tested. Some of the assays will be developed as deployable diagnostic tools. These tools will provide data on virus emergence and will assist in surveillance, development of risk assessments, and predictive modeling.