Direct visualization of HIV-1 replication intermediates shows that capsid and CPSF6 modulate HIV-1 intra-nuclear invasion and integration
Open accessAbstract
Direct visualization of HIV-1 replication would improve our understanding of the viral life cycle. We adapted established technology and reagents to develop an imaging approach, ViewHIV, which allows evaluation of early HIV-1 replication intermediates, from reverse transcription to integration. These methods permit the simultaneous evaluation of both the capsid protein (CA) and viral DNA genome (vDNA) components of HIV-1 in both the cytosol and nuclei of single cells. ViewHIV is relatively rapid, uses readily available reagents in combination with standard confocal microscopy, and can be done with virtually any HIV-1 strain and permissive cell lines or primary cells. Using ViewHIV, we find that CA enters the nucleus and associates with vDNA in both transformed and primary cells. We also find that CA's interaction with the host polyadenylation factor, CPSF6, enhances nuclear entry and potentiates HIV-1's depth of nuclear invasion, potentially aiding the virus's integration into gene-dense regions.
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CA facilitates HIV-1 integration into transcriptionally active, gene-rich regions via interacting with CPSF, which helps connect the PIC to intranuclear trafficking pathways to facilitate entry into the inner regions of the nucleus.
“Further evidence shows that CA facilitates HIV-1 integration into transcriptionally active, gene-rich regions via interacting with CPSF that in fact helps connect the PIC to intranuclear trafficking pathways to facilitate entry into the inner regions of the nucleus (Chin et al. 2015, Achuthan et al. 2018).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Chin et al. 2015
The Results section (“The polyadenylation factor CPSF6 modulates the depth of HIV-1 intra-nuclear invasion and integration”; page unavailable) reports that CA–CPSF6 interaction governs how deeply the PIC enters the nucleus and where integration occurs. The Discussion proposes that CPSF6 helps traffic the PIC to actively transcribed genes. The copy does not establish the additional “gene-rich” qualifier, and it presents the detailed trafficking mechanism as a model rather than a demonstrated pathway. (LLM, conf=0.85)
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“Some previous studies have suggested that low levels of CA are associated with nuclear complexes (14, 15, 17, 19, 20, 22) and are thought to influence integration site selection (23, 24); in these studies, the nuclear CA amounts may have been underestimated because of reduced CA epitope accessibility (25).”
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Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration
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Nuclear import of the HIV-1 core precedes reverse transcription and uncoating
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Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“…shows that CA facilitates HIV-1 integration into transcriptionally active, gene-rich regions via interacting with CPSF that in fact helps connect the PIC to intranuclear trafficking pathways to facilitate entry into the inner regions of the nucleus (Chin et al. 2015 , Achuthan et al. 2018 ).”
- Authors
- Chin, C. R., Perreira, J. M., Savidis, G., Portmann, J. M., Aker, A. M., Feeley, E. M., Smith, M. C., & Brass, A. L.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Harvard University (US)
- Corresponding author
- Brass, Abraham L.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 13
- Issue
- 8
- Pages
- 1717-1731
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5026322
- OpenAlex
- W2176753208
- Cited by
- 166
- References
- 3
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 11 · 2023: 9 · 2022: 17 · 2021: 23 · 2020: 19 · 2019: 17 · 2018: 18 · 2017: 13 · 2016: 15
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Massachusetts Center for AIDS Research
- Bill and Melinda Gates Foundation
- Burroughs Wellcome Fund
- NIH (1R01AI091786)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1 replication, capsid protein, CPSF6, viral DNA integration, nuclear entry, single-cell imaging, reverse transcription, polyadenylation, viral life cycle, primary cells
- MeSH terms
- Capsid, Cell Nucleus, Cytosol, DNA Replication, HeLa Cells, Humans, Virus Replication, HIV-1, HIV Infections, Virus Integration, Genome, Viral, Capsid Proteins, mRNA Cleavage and Polyadenylation Factors, Cell Line, Tumor, Reverse Transcription
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