Evidence map›Paper›PMID 32753492›Full record

ArticlemBio2020

HIV Vpr Modulates the Host DNA Damage Response at Two Independent Steps to Damage DNA and Repress Double-Strand DNA Break Repair.

Donna Li, Andrew Lopez, Carina Sandoval, Randilea Nichols Doyle, Oliver I Fregoso

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mBio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

29 citing papers in PubMed, 34 citations in OpenAlex.

  1. Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026
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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

5 authors at 1 institution in 1 country.

Donna Li *Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Andrew Lopez *Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Carina SandovalDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Randilea Nichols DoyleDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA.
Oliver I FregosoDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA ofregoso@mednet.ucla.edu.ORCID 0000-0003-3087-3374
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Defining the regulation of double-strand DNA break repair by HIV VprR01AI147837 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREGOSO, OLIVER I · 2019 to 2023
$1.9M
Regulation of HIV-1 and related lentiviruses by the DNA damage responseK22AI122824 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREGOSO, OLIVER I · 2016 to 2017
$267k
NCI NIH HHS P30 CA016042NIAID NIH HHS K22 AI122824NIAID NIH HHS R01 AI147837NIAID NIH HHS T32 AI007323NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

The DNA damage response (DDR) is a signaling cascade that is vital to ensuring the fidelity of the host genome in the presence of genotoxic stress. Growing evidence has emphasized the importance of both activation and repression of the host DDR by diverse DNA and RNA viruses. Previous work has shown that HIV-1 is also capable of engaging the host DDR, primarily through the conserved accessory protein Vpr. However, the extent of this engagement has remained unclear. Here, we show that HIV-1 and HIV-2 Vpr directly induce DNA damage and stall DNA replication, leading to the activation of several markers of double- and single-strand DNA breaks. Despite causing damage and activating the DDR, we found that Vpr represses the repair of double-strand breaks (DSB) by inhibiting homologous recombination (HR) and nonhomologous end joining (NHEJ). Mutational analyses of Vpr revealed that DNA damage and DDR activation are independent from repression of HR and Vpr-mediated cell cycle arrest. Moreover, we show that repression of HR does not require cell cycle arrest but instead may precede this long-standing enigmatic Vpr phenotype. Together, our data uncover that Vpr globally modulates the host DDR at at least two independent steps, offering novel insight into the primary functions of lentiviral Vpr and the roles of the DNA damage response in lentiviral replication.

Indexed as

DNADNA Breaks, Double-StrandedDNA RepairCell Line, TumorHEK293 CellsHIV-1HIV-2HIV InfectionsHost-Pathogen InteractionsHumansOsteosarcomaVirus Replicationvpr Gene Products, Human Immunodeficiency VirusDNAvpr Gene Products, Human Immunodeficiency VirusDNA damageDNA damage checkpointsDNA damage responseDNA replicationHIVHIV-1HIV-2homologous recombinationhost-pathogen interactionshuman immunodeficiency viruslentivirusesretrovirusesRNA virusvirus-host interactionsVpr

Identifiers

PMID32753492
PMCPMC7407082
OpenAlexW3047099797

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.