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Cited by 57HIV Research and TreatmentVirus-based gene therapy researchHIV/AIDS drug development and treatment

HIV capsid and integration targeting

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Engelman, Alan N.·2021·Viruses
DOI 10.3390/v13010125PMC PMC7830116
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Abstract

Integration of retroviral reverse transcripts into the chromosomes of the cells that they infect is required for efficient viral gene expression and the inheritance of viral genomes to daughter cells. Before integration can occur, retroviral reverse transcription complexes (RTCs) must access the nuclear environment where the chromosomes reside. Retroviral integration is non-random, with different types of virus-host interactions impacting where in the host chromatin integration takes place. Lentiviruses such as HIV efficiently infect interphase cells because their RTCs have evolved to usurp cellular nuclear import transport mechanisms, and research over the past decade has revealed specific interactions between the HIV capsid protein and nucleoporin (Nup) proteins such as Nup358 and Nup153. The interaction of HIV capsid with cleavage and polyadenylation specificity factor 6 (CPSF6), which is a component of the cellular cleavage and polyadenylation complex, helps to dictate nuclear import as well as post-nuclear RTC invasion. In the absence of the capsid-CPSF6 interaction, RTCs are precluded from reaching nuclear speckles and gene-rich regions of chromatin known as speckle-associated domains, and instead mis-target lamina-associated domains out at the nuclear periphery. Highlighting this area of research, small molecules that inhibit capsid-host interactions important for integration site targeting are highly potent antiviral compounds.

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  • Mutations in HIV-1 CA and its interactions with cyclophilin do not inhibit viral integration but favor integration into genomic regions that are not transcriptionally active, as opposed to wild-type virus typically integrating into transcriptionally active regions.

    “Evidence toward this has been drawn from experiments that have shown that mutations in HIV-1 CA and its interactions with cyclophilin do not inhibit viral integration but favor integration into the genomic regions that are not transcriptionally active, as opposed to wild-type virus typically integrating into the transcriptionally active regions (Lewinski et al. 2006, Schaller et al. 2011, Engelman”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Engelman 2021

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  • Gag-derived protein(s), especially CA, play an important role during retroviral integration.

    “For example, it has been suggested that Gag-derived protein(s), especially CA, plays an important role during retroviral integration.”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Engelman 2021

    The Introduction (page unavailable) says that CA helps direct HIV-1 integration to active genes, and Section 2 identifies CA as derived from Gag. The source supports a role for Gag-derived CA in HIV-1 integration targeting, but the claim extends that role to retroviral integration generally. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Engelman, A. N.
Affiliations
Harvard University (US)
Corresponding author
Engelman, Alan N.
ORCID
Engelman, Alan N.
Venue
Viruses
Publisher
MDPI AG
Published
2021-01-18
Volume
13
Issue
1
Pages
125
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v13010125
PMC
PMC7830116
OpenAlex
W3125593851
Cited by
57
References
16
Citations by year
2026: 9 · 2025: 12 · 2024: 7 · 2023: 12 · 2022: 9 · 2021: 8
FWCI
1.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (R01AI052014, R37AI039394, P50AI150481)
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
retroviral integration, nuclear import, nucleoporins, Nup358, Nup153, CPSF6, nuclear speckles, lamina-associated domains, small-molecule antivirals
MeSH terms
Capsid, Chromatin, Humans, Protein Binding, Structure-Activity Relationship, HIV-1, HIV Infections, Virus Integration, Active Transport, Cell Nucleus, Nuclear Pore Complex Proteins, Capsid Proteins, Host-Pathogen Interactions

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