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Cytoplasmic CPSF6 regulates HIV-1 capsid trafficking and infection in a cyclophilin A-dependent manner
- Source :
- mBio, mBio, Vol 12, Iss 2 (2021)
- Publication Year :
- 2021
- Publisher :
- American Society for Microbiology, 2021.
-
Abstract
- 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.<br />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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- mBio, mBio, Vol 12, Iss 2 (2021)
- Accession number :
- edsair.doi.dedup.....ea2ee0b80b1ffc3d200d4e467810e8f1