Evidence map›Paper›PMID 33270250›Full record

ArticleThe EMBO journal2021

Clustering and reverse transcription of HIV-1 genomes in nuclear niches of macrophages.

Elena Rensen, Florian Mueller, Viviana Scoca, Jyotsana J Parmar, Philippe Souque, Christophe Zimmer, Francesca Di Nunzio

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

67 citing papers in PubMed, 90 citations in OpenAlex.

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  12. Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice.Proceedings of the National Academy of Sciences of the United States of America · 2025
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7 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

7 authors at 2 institutions in 1 country.

Elena RensenImaging and Modeling Unit, Institut Pasteur, UMR 3691 CNRS, C3BI USR 3756 IP CNRS, Paris, France.
Florian MuellerImaging and Modeling Unit, Institut Pasteur, UMR 3691 CNRS, C3BI USR 3756 IP CNRS, Paris, France.ORCID 0000-0002-9622-4396
Viviana ScocaMolecular Virology and Vaccinology, Institut Pasteur, Paris, France.
Jyotsana J ParmarImaging and Modeling Unit, Institut Pasteur, UMR 3691 CNRS, C3BI USR 3756 IP CNRS, Paris, France.
Philippe SouqueMolecular Virology and Vaccinology, Institut Pasteur, Paris, France.
Christophe ZimmerImaging and Modeling Unit, Institut Pasteur, UMR 3691 CNRS, C3BI USR 3756 IP CNRS, Paris, France.ORCID 0000-0001-9910-1589
Francesca Di NunzioMolecular Virology and Vaccinology, Institut Pasteur, Paris, France.ORCID 0000-0003-2879-3164
Centre National de la Recherche Scientifique · FRInstitut Pasteur · FR

Funding

Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) ECTZ4469Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) ECTZ74440Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) ECTZ88162Fondation pour la Recherche Médicale (FRM) DEQ 20150331762Institut Carnot Pasteur MSSidaction VIH20170718001
6 · The paper itself

Abstract

In order to replicate, human immunodeficiency virus (HIV-1) reverse-transcribes its RNA genome into DNA, which subsequently integrates into host cell chromosomes. These two key events of the viral life cycle are commonly viewed as separate not only in time, but also in cellular space, since reverse transcription (RT) is thought to be completed in the cytoplasm before nuclear import and integration. However, the spatiotemporal organization of the early viral replication cycle in macrophages, the natural non-dividing target cells that constitute reservoirs of HIV-1 and an obstacle to curing AIDS, remains unclear. Here, we demonstrate that infected macrophages display large nuclear foci of viral DNA (vDNA) and viral RNA, in which multiple viral genomes cluster together. These clusters form in the absence of chromosomal integration, sequester the paraspeckle protein CPSF6, and localize to nuclear speckles. Surprisingly, these viral RNA clusters consist mostly of genomic, incoming RNA, both in cells where reverse transcription is pharmacologically suppressed and in untreated cells. We demonstrate that following temporary inhibition, reverse transcription can resume in the nucleus and lead to vDNA accumulation in these clusters. We further show that nuclear reverse transcription can result in transcription-competent viral DNA. These findings change our understanding of the early HIV-1 replication cycle and may have implications for addressing HIV-1 persistence.

Indexed as

Active Transport, Cell NucleusCell LineCell NucleusCluster AnalysisCytoplasmDNA, ViralGenome, ViralHEK293 CellsHIV-1HIV InfectionsHumansMacrophagesReverse TranscriptionRNA, ViralTHP-1 CellsVirus ReplicationDNA, ViralRNA, ViralHIV-1macrophagesnuclear importnuclear specklesreverse transcription

Identifiers

PMID33270250
PMCPMC7780146
OpenAlexW3106634380

What OpenQuestion holds

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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.