Evidence map›Paper›PMID 24409278›Full record

ArticlePloS one2014

Decreased mutation frequencies among immunoglobulin G variable region genes during viremic HIV-1 infection.

Elisabeth Bowers, Ronald W Scamurra, Anil Asrani, Lydie Beniguel, Samantha MaWhinney, Kathryne M Keays, Joseph R Thurn, Edward N Janoff

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 16 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

8 authors at 6 institutions in 2 countries.

Elisabeth BowersMucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America ; Infectious Disease Division, University of Colorado Denver, Aurora, Colorado, United States of America ; Department of Microbiology, University of Colorado Denver, Aurora, Colorado, United States of America ; Denver Veterans Affairs Medical Center, Denver, Colorado, United States of America.
Ronald W ScamurraMinneapolis VA Health Care System, University of Minnesota, Minneapolis, Minnesota, United States of America.
Anil AsraniMinneapolis VA Health Care System, University of Minnesota, Minneapolis, Minnesota, United States of America.
Lydie BeniguelGIMAP EA 3064, Faculté de Médecine, Université Jean Monnet, Saint Etienne, France.
Samantha MaWhinneyMucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America ; Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America.
Kathryne M KeaysMucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America ; Infectious Disease Division, University of Colorado Denver, Aurora, Colorado, United States of America.
Joseph R ThurnMinneapolis VA Health Care System, University of Minnesota, Minneapolis, Minnesota, United States of America.
Edward N JanoffMucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America ; Infectious Disease Division, University of Colorado Denver, Aurora, Colorado, United States of America ; Department of Microbiology, University of Colorado Denver, Aurora, Colorado, United States of America ; Denver Veterans Affairs Medical Center, Denver, Colorado, United States of America.
Denver VA Medical Center · USMinneapolis VA Health Care System · USColorado School of Public Health · USUniversité Jean Monnet · FRUniversity of Colorado Denver · USUniversity of Minnesota · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
U of Colorado Center for AIDS ResearchP30AI054907 · NIAID · UNIVERSITY OF COLORADO DENVER · PI CAMPBELL, THOMAS B · 2003 to 2008
$9.6M
Mechanisms of Impaired HIV-associated B cell and Pneumococcal Vaccine responsesR01AI108479 · NIAID · UNIVERSITY OF COLORADO DENVER · PI JANOFF, EDWARD N · 2014 to 2018
$2.3M
ORAL AND MUCOSAL ANTIBODY VH GENES AND HIV-1 INFECTIONF32DE005703 · NIDCR · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SCAMURRA, RONALD W · 1997 to 1999
–
NCI NIH HHS P30 CA046934NCI NIH HHS P30CA046934NIAID NIH HHS P30 AI054907NIAID NIH HHS R01 AI108479NIDCR NIH HHS F32 DE005703NIDCR NIH HHS F32DE005703-01PHS HHS R01A10495752-01
6 · The paper itself

Abstract

BACKGROUND/

objectiveHIV-1 infection is complicated by high rates of opportunistic infections against which specific antibodies contribute to immune defense. Antibody function depends on somatic hypermutation (SHM) of variable regions of immunoglobulin heavy chain genes (VH-D-J). We characterized the frequency of SHM in expressed IgG mRNA immunoglobulin transcripts from control and HIV-1-infected patients.

designWe compared utilization of genes in the most prominent VH family (VH3) and mutation frequencies and patterns of cDNA from VH3-IgG genes from 10 seronegative control subjects and 21 patients with HIV-1 infection (6 without and 15 patients with detectable plasma viremia).

methodsUnique IgG VH3 family cDNA sequences (n = 1,565) were PCR amplified, cloned, and sequenced from blood. Sequences were analyzed using online (Vbase) and in-house immunoglobulin alignment resources.

resultsMutation frequencies in the antigen-binding hypervariable complementarity determining regions (CDR1/2) of IgG class-switched B cells were lower among viremic HIV-1-infected patients vs. controls for nucleotides (CDR1/2: 10±5% vs. 13.5±6%, p = 0.03) and amino acids (CDR: 20%±10 vs. 25%±12, p = 0.02) and in structural framework regions. Mutation patterns were similar among groups. The most common VH3 gene, VH3-23, was utilized less frequently among viremic HIV-1-infected patients (p = 0.03), and overall, mutation frequencies were decreased in nearly all VH3 genes compared with controls.

conclusionsB cells from HIV-1-infected patients show decreased mutation frequencies, especially in antigen-binding VH3 CDR genes, and selective defects in gene utilization. Similar mutation patterns suggest defects in the quantity, but not quality, of mutator activity. Lower levels of SHM in IgG class-switched B cells from HIV-1-infected patients may contribute to the increased risk of opportunistic infections and impaired humoral responses to preventative vaccines.

Indexed as

MutationViremiaAdultAmino Acid MotifsAmino Acid SubstitutionCase-Control StudiesComplementarity Determining RegionsFemaleGene ExpressionHIV-1HIV AntibodiesHIV InfectionsHumansImmunoglobulin GImmunoglobulin Variable RegionMaleComplementarity Determining RegionsHIV AntibodiesImmunoglobulin GImmunoglobulin Variable Region

Identifiers

PMID24409278
PMCPMC3883639
OpenAlexW2048219375

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Registered trials

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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.