The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration
Open accessAbstract
HIV-1 integration into the host genome favors actively transcribed genes. Prior work indicated that the nuclear periphery provides the architectural basis for integration site selection, with viral capsid-binding host cofactor CPSF6 and viral integrase-binding cofactor LEDGF/p75 contributing to selection of individual sites. Here, by investigating the early phase of infection, we determine that HIV-1 traffics throughout the nucleus for integration. CPSF6-capsid interactions allow the virus to bypass peripheral heterochromatin and penetrate the nuclear structure for integration. Loss of interaction with CPSF6 dramatically alters virus localization toward the nuclear periphery and integration into transcriptionally repressed lamina-associated heterochromatin, while loss of LEDGF/p75 does not significantly affect intranuclear HIV-1 localization. Thus, CPSF6 serves as a master regulator of HIV-1 intranuclear localization by trafficking viral preintegration complexes away from heterochromatin at the periphery toward gene-dense chromosomal regions within the nuclear interior.
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“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 [85]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Another important host factor identified in retroviral integration is CPSF6 that facilitates targeting of the HIV-1 PICs to transcriptionally active regions of the genome found deep within the center of the nucleus (Rasheedi et al. 2016, Achuthan et al. 2018, Singh et al. 2022a).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Achuthan et al. 2018
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In the citing paper
“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 [85]
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“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 Achuthan et al. 2018
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The Sequence Alignment/Map format and SAMtools
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Pertea, M., Kim, D., Pertea, G. M., Leek, J. T., & Salzberg, S. L. (2016) · Nature Protocols · doi:10.1038/nprot.2016.095 · Cited by 6,783
Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions
Guelen, L., Pagie, L., Brasset, É., Meuleman, W. R. A., Faza, M. B., Talhout, W., Eussen, B. H. J., de Klein, A., Wessels, L. F. A., de Laat, W. L., et al. (2008) · Nature · doi:10.1038/nature06947 · Cited by 2,042
HIV-1 Integration in the Human Genome Favors Active Genes and Local Hotspots
Schröder, A. R. W., Shinn, P., Chen, H., Berry, C., Ecker, J. R., & Bushman, F. (2002) · Cell · doi:10.1016/s0092-8674(02)00864-4 · Cited by 1,832
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Singh, P., Li, W., Bedwell, G., Fadel, H., Poeschla, E., & Engelman, A. (2022) · Viruses · doi:10.3390/v14091883 · Cited by 13
Self-citationBeyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
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
“…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 ).”
Metadata
- Authors
- Achuthan, V., Perreira, J. M., Sowd, G. A., Puray-Chavez, M., McDougall, W. M., Paulucci-Holthauzen, A., Wu, X., Fadel, H. J., Poeschla, E. M., Multani, A. S., Hughes, S. H., Sarafianos, S. G., Brass, A. L., & Engelman, A. N.
- Affiliations
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- The University of Texas MD Anderson Cancer Center (US)
- Leidos Biomedical Research Inc. (United States) (US)
- Mayo Clinic (US)
- University of Colorado Anschutz (US)
- National Cancer Institute (US)
- University of Missouri (US)
- Corresponding author
- Brass, Abraham L.
- Engelman, Alan N.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 24
- Issue
- 3
- Pages
- 392-404.e8
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC6368089
- OpenAlex
- W2889370079
- Cited by
- 205
- References
- 78
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 33 · 2023: 20 · 2022: 22 · 2021: 34 · 2020: 29 · 2019: 22 · 2018: 2
- FWCI
- 11.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01 AI052014, R01 AI077344, P30 AI060354, T32 AI007245)
- NCI
- Bill and Melinda Gates Foundation (OPP1097381)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- HIV-1, capsid, CPSF6, LEDGF/p75, preintegration complex, nuclear trafficking, heterochromatin, nuclear periphery, viral DNA integration, host cofactors
- MeSH terms
- Capsid, Cell Nucleus, DNA, Viral, Humans, Protein Binding, Virus Replication, HIV-1, HIV Infections, Virus Integration, Intercellular Signaling Peptides and Proteins, mRNA Cleavage and Polyadenylation Factors, Host-Pathogen Interactions
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