Evidence map›Paper›PMID 36114511›Full record

ArticleRetrovirology2022

Replication-competent HIV-1 in human alveolar macrophages and monocytes despite nucleotide pools with elevated dUTP.

Junru Cui, Mesfin Meshesha, Natela Churgulia, Christian Merlo, Edward Fuchs, Jennifer Breakey, Joyce Jones, James T Stivers

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

Article in Retrovirology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
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

8 authors at 2 institutions in 1 country.

Junru CuiDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205-2185, USA.
Mesfin MesheshaDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205-2185, USA.
Natela ChurguliaDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205-2185, USA.
Christian MerloDivision of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, 1830 E. Monument Street/5th Floor, Baltimore, MD, 21205, USA.
Edward FuchsDivision of Clinical Pharmacology, Drug Development Unit, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 569, Baltimore, MD, 21287, USA.
Jennifer BreakeyDivision of Clinical Pharmacology, Drug Development Unit, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 569, Baltimore, MD, 21287, USA.
Joyce JonesDivision of Infectious Diseases, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Baltimore, MD, 21205, USA.
James T StiversDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205-2185, USA. jstivers@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Uracil Damage Recognition by Uracil DNA GlyocosylaseR01GM056834 · NIGMS · UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE · PI STIVERS, JAMES T. · 1998 to 2021
$8.3M
Fate of Invisible U/A Base Pairs Within HIV DNA in Myeloid Phagocytic CellsR01AI124777 · NIAID · JOHNS HOPKINS UNIVERSITY · PI STIVERS, JAMES T. · 2016 to 2020
$2.0M
NIAID NIH HHS R01 AI124777NIGMS NIH HHS R01 GM056834
6 · The paper itself

Abstract

backgroundAlthough CD4

resultsAs compared to in vitro differentiated MDM, AM from normal donors had sixfold lower levels of dTTP and a sixfold increased dUTP/dTTP, indicating a highly restrictive dNTP pool for reverse transcription. Expression of uracil DNA glycosylase (UNG) was eightfold lower in AM compared to the already low levels in MDM. Accordingly, ~ 80% of HIV proviruses contained dUMP, which persisted for at least 14-days due to low UNG excision activity. Unlike MDM, AM expression levels of UNG and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) increased over 14 days post-HIV infection, while dUTP nucleotidohydrolase (DUT) expression decreased. These AM-specific effects suggest a restriction response centered on excising uracil from viral DNA copies and increasing relative dUTP levels. Despite the restrictive nucleotide pools, we detected rare replication competent HIV in AM, peripheral MC, and CD4

conclusionsThese findings indicate that the potential integration block of incorporated dUMP is not realized during in vivo infection of AM and MC due to the near absence of UBER activity. In addition, the increased expression of UNG and SAMHD1 in AM post-infection is too slow to prevent integration. Accordingly, dUMP persists in integrated viruses, which based on in vitro studies, can lead to transcriptional silencing. This possible silencing outcome of persistent dUMP could promote viral latency until the repressive effects of viral dUMP are reversed.

Indexed as

HIV-1HIV InfectionsDNA, ViralHumansMacrophages, AlveolarMonocytesNucleotidesSAM Domain and HD Domain-Containing Protein 1UracilUracil-DNA GlycosidaseVirus ReplicationDNA, ViralNucleotidesSAM Domain and HD Domain-Containing Protein 1UracilUracil-DNA GlycosidaseAlveolar macrophageHuman HIV-1 infectionMonocyteNucleotide poolsReplication competent virusUracil base excision repair

Identifiers

PMID36114511
PMCPMC9482235
OpenAlexW4296068971

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.