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Research Project: Pathogenesis, Epidemiology, and Control Measures for Rift Valley Fever

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Title: Rift Valley Fever virus Gn V5-epitope tagged virus enables identification of UBR4 as a Gn interacting protein that facilitates Rift Valley Fever virus production

Author
item BRACCI, NICOLE - Virginia Polytechnic Institution & State University
item DE LA FUENTE, CYNTHIA - National Institutes Of Health (NIH)
item SALEEM, SAHAR - George Mason University
item PINKHAM, CHELSEA - George Mason University
item NARAYANAN, AARTHI - George Mason University
item GARCIA-SASTRE, ADOLFO - The Icahn School Of Medicine At Mount Sinai
item BALARAMAN, VELMURUGAN - Kansas State University
item RICHT, JUERGEN - Kansas State University
item Wilson, William
item KEHN-HALL, KYLENE - George Mason University

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2021
Publication Date: 1/7/2022
Citation: Bracci, N., De La Fuente, C., Saleem, S., Pinkham, C., Narayanan, A., Garcia-Sastre, A., Balaraman, V., Richt, J.A., Wilson, W.C., Kehn-Hall, K. 2022. Rift Valley Fever virus Gn V5-epitope tagged virus enables identification of UBR4 as a Gn interacting protein that facilitates Rift Valley Fever virus production. Virology. 567:65-76. https://doi.org/10.1016/j.virol.2021.12.010.
DOI: https://doi.org/10.1016/j.virol.2021.12.010

Interpretive Summary: The mosquito transmitted Rift Valley fever virus (RVFV) causes significant disease in humans and animals. Outbreaks in the the endemic in Sub-Saharan Africa result in substantial socioeconomic losses. In this study two marked viruses were produced using recombinant technology and a vaccine strain of the virus. These virus constructs were used to investigate virus interactions with host proteins. A specific host protein was found to be important in virus production in the host. This information could be used in future studies to develop better strategies to control RVFV infection and/or transmission.

Technical Abstract: Rift Valley fever virus (RVFV) is an arbovirus that was first reported in the Rift Valley of Kenya which causes significant disease in humans and livestock. RVFV is a tri-segmented, negative-sense RNA virus consisting of a S, M, and L segments with the M segment encoding the glycoproteins Gn and Gc. Host factors that interact with Gn are largely unknown. To this end, two viruses containing a V5-epitope tag on the Gn protein (V5Gn105 and V5Gn229) were generated using RVFV MP-12 as a backbone. The V5-tag insertion minimally impacted Gn functionality as measured by replication kinetics, Gn localization, and antibody neutralization assays. A proteomics-based approach was used to identify novel Gn-binding host proteins. Immunoprecipitation followed by mass spectrometry identified the E3 ubiquitin-protein ligase, UBR4, as a Gn-binding partner. Depletion of UBR4 resulted in a significant decrease in RVFV titers and a reduction in viral RNA production.