HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains
Open accessAbstract
The early steps of HIV-1 infection, such as uncoating, reverse transcription, nuclear import, and transport to integration sites are incompletely understood. Here, we imaged nuclear entry and transport of HIV-1 replication complexes in cell lines, primary monocyte-derived macrophages (MDMs) and CD4 + T cells. We show that viral replication complexes traffic to and accumulate within nuclear speckles and that these steps precede the completion of viral DNA synthesis. HIV-1 transport to nuclear speckles is dependent on the interaction of the capsid proteins with host cleavage and polyadenylation specificity factor 6 (CPSF6), which is also required to stabilize the association of the viral replication complexes with nuclear speckles. Importantly, integration site analyses reveal a strong preference for HIV-1 to integrate into speckle-associated genomic domains. Collectively, our results demonstrate that nuclear speckles provide an architectural basis for nuclear homing of HIV-1 replication complexes and subsequent integration into associated genomic loci.
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Under normal infection conditions, HIV-1 pre-integration complexes colocalize with nuclear speckles and strongly favor SPADs for integration while avoiding LADs.
“Under normal infection conditions, HIV-1 PICs colocalized with nuclear speckles and strongly favoured SPADs for integration while avoiding LADs84.”
From Structure and function of retroviral integrase (2022) · cites this paper as [84]
The Results section (‘HIV-1 integrates into speckle-associated genomic DNA’; page unavailable) reports that HIV-1 replication complexes accumulate in nuclear speckles and that integration strongly favors SPADs across cell types. The Discussion mentions LAD association for recurrent integration genes in the absence of CA–CPSF6 interaction, but does not establish that HIV-1 avoids LADs under normal infection conditions. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCPSF6 plays a critical role in regulating nuclear pre-integration complex incursion.
“In addition to its role in nuclear import, CPSF6 plays a critical role in regulating nuclear PIC incursion.”
From Structure and function of retroviral integrase (2022) · cites this paper as [84]
The Results section (“Relocation outside of NSs diminishes nuclear VRC stability”; page unavailable) suggests that CPSF6 is involved in transporting HIV-1 viral replication complexes to nuclear speckles. The Discussion (page unavailable) is more cautious: it says CPSF6 and/or other factors may tether the complexes there. These passages support a role in intranuclear positioning, but not the stronger assertion that CPSF6 itself plays a critical role in regulating nuclear PIC incursion. (LLM, conf=0.81)
Experimental — accuracy not yet measuredIn CPSF6 knockout cells, pre-integration complexes congregate at the nuclear periphery and target LADs for integration while losing the preference for SPADs.
“In CPSF6 knockout cells, PICs congregated at the nuclear periphery and uncharacteristically targeted LADs for integration while losing the preference for SPADs84,85.”
From Structure and function of retroviral integrase (2022) · cites this paper as [84]
The Results section ('HIV-1 integrates into speckle-associated genomic DNA'; page unavailable) reports that HIV-1 disfavored SPAD integration in CPSF6-knockout cells. The Discussion (page unavailable) says CPSF6-negative recurrent integration genes associate with LADs at the nuclear periphery, citing a prior report. These passages do not establish that pre-integration complexes congregated at the nuclear periphery in knockout cells or that knockout cells broadly targeted LADs for integration. (LLM, conf=0.84)
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May I Help You with Your Coat? HIV-1 Capsid Uncoating and Reverse Transcription
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Brief Histories of Retroviral Integration Research and Associated International Conferences
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Self-citation
- Authors
- Francis, A. C., Marin, M., Singh, P. K., Achuthan, V., Prellberg, M. J., Palermino-Rowland, K., Lan, S., Tedbury, P. R., Sarafianos, S. G., Engelman, A. N., & Melikyan, G. B.
- Affiliations
- Emory University (US)
- Harvard University (US)
- Corresponding author
- Francis, Ashwanth C.
- Melikyan, Gregory B.
- ORCID
- Venue
- Nature Communications
- Published
- 2020-07-14
- Volume
- 11
- Issue
- 1
- Pages
- 3505-3505
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7360574
- OpenAlex
- W3042510281
- Cited by
- 159
- References
- 75
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 27 · 2023: 20 · 2022: 32 · 2021: 29 · 2020: 7
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-11-26)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01 AI129862, R01 AI052014, R01 AI148382, R01 AI120860, U54 AI150472)
- 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, nuclear speckles, viral replication complex, viral integration, CPSF6, capsid protein, nuclear transport, monocyte-derived macrophages, CD4+ T cells, nuclear organization, viral uncoating, reverse transcription
- MeSH terms
- Cell Nucleus, Humans, Microscopy, Fluorescence, Virology, Virus Replication, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Virus Integration, Genome, Viral, Capsid Proteins, Host-Pathogen Interactions, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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