Evidence map›Paper›PMID 22911005›Full record

ArticlePLoS pathogens2012

Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.

Matthew J Pace, Erin H Graf, Luis M Agosto, Angela M Mexas, Frances Male, Troy Brady, Frederic D Bushman, Una O'Doherty

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed
6.3field-weighted citation impact, top 2% 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

108 citing papers in PubMed, 141 citations in OpenAlex.

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  14. TILDA: Tat/Rev Induced Limiting Dilution Assay.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
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48 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

8 authors at 1 institution in 1 country.

Matthew J PaceDepartment of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Erin H Graf
Luis M Agosto
Angela M Mexas
Frances Male
Troy Brady
Frederic D Bushman
Una O'Doherty
University of Pennsylvania · US

Funding

Molecular Virology and Systems Biology Screening CoreP01AI090935 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YOUNG, JOHN A T · 2010 to 2014
$20.4M
Ongoing replication may occur on HAARTR21AI087461 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI O'DOHERTY, UNA T · 2010 to 2011
$431k
BIOLOGICAL AND MOLECULAR STUDY OF THE GENE PRODUCT OF THE CCR5DELTA32 ALLELEZ01AI000762 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI SCALA, G · 1997 to 1998
–
NIAID NIH HHS AI00762NIAID NIH HHS AI087461NIAID NIH HHS P01 AI090935NIAID NIH HHS R21 AI087461
6 · The paper itself

Abstract

Despite the effectiveness of highly active antiretroviral therapy (HAART) in treating individuals infected with HIV, HAART is not a cure. A latent reservoir, composed mainly of resting CD4+T cells, drives viral rebound once therapy is stopped. Understanding the formation and maintenance of latently infected cells could provide clues to eradicating this reservoir. However, there have been discrepancies regarding the susceptibility of resting cells to HIV infection in vitro and in vivo. As we have previously shown that resting CD4+T cells are susceptible to HIV integration, we asked whether these cells were capable of producing viral proteins and if so, why resting cells were incapable of supporting productive infection. To answer this question, we spinoculated resting CD4+T cells with or without prior stimulation, and measured integration, transcription, and translation of viral proteins. We found that resting cells were capable of producing HIV Gag without supporting spreading infection. This block corresponded with low HIV envelope levels both at the level of protein and RNA and was not an artifact of spinoculation. The defect was reversed upon stimulation with IL-7 or CD3/28 beads. Thus, a population of latent cells can produce viral proteins without resulting in spreading infection. These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response.

Indexed as

Virus LatencyCD28 AntigensCD3 ComplexCD4-Positive T-LymphocytesCells, Culturedenv Gene Products, Human Immunodeficiency Virusgag Gene Products, Human Immunodeficiency VirusGene Expression Regulation, ViralHIV-1HIV InfectionsHumansInterleukin-17Interleukin-7Macrophage Inflammatory ProteinsVirus ReplicationCD28 AntigensCD3 Complexenv Gene Products, Human Immunodeficiency Virusgag Gene Products, Human Immunodeficiency VirusInterleukin-17Interleukin-7Macrophage Inflammatory Proteins

Identifiers

PMID22911005
PMCPMC3406090
OpenAlexW2008301697

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.