Evidence map›Paper›PMID 35758669›Full record

ArticleJournal of virology2022

Mutations in the 3'-PPT Lead to HIV-1 Replication without Integration.

Clémence Richetta, Frédéric Subra, Isabelle Malet, Hervé Leh, Charlotte Charpentier, Angela Corona, Gilles Collin, Diane Descamps, Eric Deprez, Vincent Parissi and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 24 citations in OpenAlex.

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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

14 authors at 3 institutions in 2 countries.

Clémence Richetta *LBPA, ENS Paris-Saclay, CNRS UMR8113, IDA FR3242, Université Paris-Saclay, Cachan, France.
Frédéric Subra *LBPA, ENS Paris-Saclay, CNRS UMR8113, IDA FR3242, Université Paris-Saclay, Cachan, France.
Isabelle Malet *Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP) AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, Paris, France.
Hervé LehLBPA, ENS Paris-Saclay, CNRS UMR8113, IDA FR3242, Université Paris-Saclay, Cachan, France.
Charlotte CharpentierINSERM, IAME, UMR 1137, Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France.
Angela CoronaDepartment of Life and Environmental Sciences, University of Cagliarigrid.7763.5, Cittadella Universitaria di Monserrato, Monserrato, Italy.
Gilles CollinINSERM, IAME, UMR 1137, Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France.
Diane DescampsINSERM, IAME, UMR 1137, Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Virologie, Paris, France.
Eric DeprezLBPA, ENS Paris-Saclay, CNRS UMR8113, IDA FR3242, Université Paris-Saclay, Cachan, France.
Vincent ParissiFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed, Bordeaux Cedex, France.ORCID 0000-0003-1661-7841
Vincent CalvezSorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP) AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, Paris, France.
Enzo TramontanoDepartment of Life and Environmental Sciences, University of Cagliarigrid.7763.5, Cittadella Universitaria di Monserrato, Monserrato, Italy.ORCID 0000-0002-4849-0980
Anne-Geneviève MarcelinSorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP) AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, Paris, France.
Olivier DelelisLBPA, ENS Paris-Saclay, CNRS UMR8113, IDA FR3242, Université Paris-Saclay, Cachan, France.ORCID 0000-0001-9293-2558
Centre National de la Recherche Scientifique · FRInserm · FRUniversity of Cagliari · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Integration of the reverse-transcribed genome is a critical step of the retroviral life cycle. Strand-transfer inhibitors (INSTIs) used for antiretroviral therapy inhibit integration but can lead to resistance mutations in the integrase gene, the enzyme involved in this reaction. A significant proportion of INSTI treatment failures, particularly those with second-generation INSTIs, show no mutation in the integrase gene. Here, we show that replication of a selected dolutegravir-resistant virus with mutations in the 3'-PPT (polypurine tract) was effective, although no integrated viral DNA was detected, due to the accumulation of unintegrated viral DNA present as 1-LTR circles. Our results show that mutation in the 3'-PPT leads to 1-LTR circles and not linear DNA as classically reported. In conclusion, our data provide a molecular basis to explain a new mechanism of resistance to INSTIs, without mutation of the integrase gene and highlights the importance of unintegrated viral DNA in HIV-1 replication.

Indexed as

DNA, ViralHIV-1MutationVirus IntegrationVirus ReplicationHIV InfectionsHumansDNA, ViralHIV-1integraseintegrationresistanceunintegrated viral DNA

Identifiers

PMID35758669
PMCPMC9327692
OpenAlexW4283651951

What OpenQuestion holds

Textmetadata
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.