Evidence map›Paper›PMID 33649225›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

HIV-1 cores retain their integrity until minutes before uncoating in the nucleus.

Chenglei Li, Ryan C Burdick, Kunio Nagashima, Wei-Shau Hu, Vinay K Pathak

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed
17.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

121 citing papers in PubMed, 165 citations in OpenAlex.

  1. Article
  2. Article
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  4. HIV-1 capsid interactions with Nuclear Pore Complex components support nuclear entry via affinity gradient.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Mechanistic insights into lenacapavir-induced off-pathway HIV-1 capsid assembly.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Review
  9. bioRxiv : the preprint server for biology · 2026
    Article
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  11. Review
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  19. Article
  20. Blockade ofmBio · 2025
    Article

61 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Chenglei LiViral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702.ORCID 0000-0003-2789-967X
Ryan C BurdickViral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702.
Kunio NagashimaElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702.
Wei-Shau HuViral Recombination Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702.
Vinay K PathakViral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702; pathakv@mail.nih.gov.
National Cancer Institute · USFrederick National Laboratory for Cancer Research · USLeidos (United States) · US

Funding

Viral Replication and Interactions with Host FactorsZIABC011436 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PATHAK, VINAY K. · 2012 to 2025
$12.2M
Understanding Retroviral Reverse Transcription, Recombination, and ReplicationZIABC010504 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HU, WEI-SHAU · 2009 to 2025
$5.3M
6 · The paper itself

Abstract

We recently reported that HIV-1 cores that retained >94% of their capsid (CA) protein entered the nucleus and disassembled (uncoated) near their integration site <1.5 h before integration. However, whether the nuclear capsids lost their integrity by rupturing or a small loss of CA before capsid disassembly was unclear. Here, we utilized a previously reported vector in which green fluorescent protein is inserted in HIV-1 Gag (iGFP); proteolytic processing efficiently releases GFP, some of which remains trapped inside capsids and serves as a fluid phase content marker that is released when the capsids lose their integrity. We found that nuclear capsids retained their integrity until shortly before integration and lost their GFP content marker ∼1 to 3 min before loss of capsid-associated mRuby-tagged cleavage and polyadenylation specificity factor 6 (mRuby-CPSF6). In contrast, loss of GFP fused to CA and mRuby-CPSF6 occurred simultaneously, indicating that viral cores retain their integrity until just minutes before uncoating. Our results indicate that HIV-1 evolved to retain its capsid integrity and maintain a separation between macromolecules in the viral core and the nuclear environment until uncoating occurs just before integration. These observations imply that intact HIV-1 capsids are imported through nuclear pores; that reverse transcription occurs in an intact capsid; and that interactions between the preintegration complex and LEDGF/p75, and possibly other host factors that facilitate integration, must occur during the short time period between loss of capsid integrity and integration.

Indexed as

Virus InternalizationCell Linegag Gene Products, Human Immunodeficiency VirusHIV-1HumansNucleocapsidgag Gene Products, Human Immunodeficiency Viruscapsidcore integrityHIV-1nuclear importuncoating

Identifiers

PMID33649225
PMCPMC7958386
OpenAlexW3135108410

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.