Cytoplasmic CPSF6 regulates HIV-1 capsid trafficking and infection in a cyclophilin A-dependent manner
| Autor: | Simon C. Watkins, Cheryl A. Telmer, Jinwoo Ahn, Zhou Zhong, Jiying Ning, Zandrea Ambrose, Alan Engelman, Marcel P. Bruchez, Sooin Jang, Emerson A. Boggs, Callen T. Wallace, Peijun Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
CD4-Positive T-Lymphocytes
viruses Cypa Cleavage and polyadenylation specificity factor Virus Replication Microbiology CPSF6 live-cell imaging Cyclophilin A Capsid Microtubule Virology medicine Humans Cellular localization Cell Nucleus mRNA Cleavage and Polyadenylation Factors Innate immune system human immunodeficiency virus biology Chemistry Macrophages virus diseases biology.organism_classification QR1-502 Immunity Innate Cell biology Cell nucleus HEK293 Cells medicine.anatomical_structure Cytoplasm Host-Pathogen Interactions HIV-1 Capsid Proteins Research Article microtubule HeLa Cells Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | mBio mBio, Vol 12, Iss 2 (2021) |
| Popis: | HIV is the causative agent of AIDS, which has no cure. The protein shell that encases the viral genome, the capsid, is critical for HIV replication in cells at multiple steps. Human immunodeficiency virus type 1 (HIV-1) capsid binds host proteins during infection, including cleavage and polyadenylation specificity factor 6 (CPSF6) and cyclophilin A (CypA). We observe that HIV-1 infection induces higher-order CPSF6 formation, and capsid-CPSF6 complexes cotraffic on microtubules. CPSF6-capsid complex trafficking is impacted by capsid alterations that reduce CPSF6 binding or by excess cytoplasmic CPSF6 expression, both of which are associated with decreased HIV-1 infection. Higher-order CPSF6 complexes bind and disrupt HIV-1 capsid assemblies in vitro. Disruption of HIV-1 capsid binding to CypA leads to increased CPSF6 binding and altered capsid trafficking, resulting in reduced infectivity. Our data reveal an interplay between CPSF6 and CypA that is important for cytoplasmic capsid trafficking and HIV-1 infection. We propose that CypA prevents HIV-1 capsid from prematurely engaging cytoplasmic CPSF6 and that differences in CypA cellular localization and innate immunity may explain variations in HIV-1 capsid trafficking and uncoating in CD4+ T cells and macrophages. |
| Databáze: | OpenAIRE |
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