Project Number: 3022-32000-024-000-D
Project Type: In-House Appropriated
Start Date: Nov 16, 2021
End Date: Nov 15, 2026
Objective 1: Identify factors associated with 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. • 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. Sub-objective 1.A: Identify cellular factors important for replication and pathogenesis in the vector and the mammalian host cells. Sub-objective 1.B: Examine the effects of temperature on the extrinsic incubation period of RVFV in various mosquito species. Sub-objective 1.C.: Develop deployable tools for rapid diagnosis and characterization of RFVF.
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 (OIE) 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. The objective of this study is to identify factors associated with RVFV infections, pathogenesis and maintenance in vector and animal hosts. This objective is split into three parts: 1) characterize host, vector and bunyavirus interactions associated with virus infection, 2) identify epidemiological and ecological factors affecting the inter-epidemic cycle and 3) develop means to detect and characterize emergent arboviral diseases and use these data to generate models that predict future outbreaks. The objective is addressed by the following sub-objectives. Sub-objective 1A identifies cellular factors important for virus replication and pathogenesis in disparate hosts by examining how Rho GTPases effects RVFV replication. Rho GTPases are key regulators of cytoskeleton rearrangement and play an important role in virus replication. Effects of temperature on RVFV extrinsic incubation period in two mosquito species will be examined for Sub-objective 1B. These studies will ascertain the potential of a mosquito species to maintain and transmit RVFV during the various temperatures associated with inter-epidemic periods. Sub-objective 1C will develop deployable diagnostic and next-generation sequencing assays to rapidly detect and characterize RVFV. These tools will provide data on virus emergence and will assist in surveillance, development of risk assessments, and predictive modeling.