CD4 Expression and Env Conformation Are Critical for HIV-1 Restriction by SERINC5
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- Xihe Zhang
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
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- Jing Shi
- Harbin Veterinary Research Institute, CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, Harbin, China
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- Xusheng Qiu
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
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- Qingqing Chai
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
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- Dylan A. Frabutt
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
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- Richard C. Schwartz
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
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- Yong-Hui Zheng
- Harbin Veterinary Research Institute, CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, Harbin, China
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- Frank Kirchhoff
- editor
説明
<jats:p>Restriction factors provide the first line of defense against retrovirus infection by posing several blocks to the viral replication cycle. SERINC5 is a novel restriction factor that strongly blocks HIV-1 entry, although it is counteracted by Nef. Currently, it is still unclear how HIV-1 entry is blocked by SERINC5. Notably, this entry block is dependent on viral Env proteins. Laboratory-adapted HIV-1 strains are sensitive, whereas primary isolates are highly resistant to SERINC5. Env proteins mediate virus entry via extensive conformational rearrangements from a closed ground state to a CD4-bound open state. We detected Env-Env associations and Env-SERINC5 interactions in live cells by a novel bimolecular fluorescence assay. We demonstrate that CD4 expression increases the Env sensitivity to SERINC5 and allows SERINC5 to dissociate the Env complex, suggesting that SERINC5 restriction is dependent on Env conformation. Our results provide new insights into the poorly defined Env-dependent SERINC5 antiviral mechanism.</jats:p>
収録刊行物
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- Journal of Virology
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Journal of Virology 93 (14), 2019-07-15
American Society for Microbiology
