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

被引:3
作者
Bracci, Nicole [1 ,3 ]
de la Fuente, Cynthia [2 ,3 ]
Saleem, Sahar [3 ]
Pinkham, Chelsea [3 ]
Narayanan, Aarthi [3 ]
Garcia-Sastre, Adolfo [4 ]
Balaraman, Velmurugan [5 ]
Richt, Juergen A. [5 ]
Wilson, William [6 ]
Kehn-Hall, Kylene [1 ,3 ,7 ]
机构
[1] Virginia Polytech Inst & State Univ, Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, Integrated Life Sci Bldg,1981 Kraft Dr, Blacksburg, VA 24060 USA
[2] NIAID, NIH, DEA, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] George Mason Univ, Natl Ctr Biodef & Infect Dis, Sch Syst Biol, Fairfax, VA 22030 USA
[4] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
[5] Kansas State Univ, Coll Vet Med, Dept Diagnost Med Pathobiol, Manhattan, KS 66506 USA
[6] ARS, Natl Bio & Agrodef Facil, USDA, Manhattan, KS USA
[7] Virginia Polytech Inst & State Univ, Ctr Zoonot & Arthropod Borne Pathogens, Blacksburg, VA 24060 USA
基金
美国国家卫生研究院;
关键词
Rift valley fever virus; Glycoproteins; UBR4; Gn; ENVELOPE GLYCOPROTEINS; M SEGMENT; VACCINATION; STRATEGY; ENTRY; MOTIF;
D O I
10.1016/j.virol.2021.12.010
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 L, M, and S 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 an epitope tag (V5) on the Gn protein in position 105 or 229 (V5Gn105 and V5Gn229) were generated using the RVFV MP-12 vaccine strain 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, including the E3 ubiquitin-protein ligase, UBR4. Depletion of UBR4 resulted in a significant decrease in RVFV titers and a reduction in viral RNA production.
引用
收藏
页码:65 / 76
页数:12
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