Dataset Information

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

ABSTRACT:

Background/objective

HIV-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.

Design

We 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).

Methods

Unique 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.

Results

Mutation 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.

Conclusions

B 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.

SUBMITTER: Bowers E

PROVIDER: S-EPMC3883639 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Bowers Elisabeth E Scamurra Ronald W RW Asrani Anil A Beniguel Lydie L MaWhinney Samantha S Keays Kathryne M KM Thurn Joseph R JR Janoff Edward N EN

PloS one 20140107 1

<h4>Background/objective</h4>HIV-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.<h4>Design</h4>We compared utilization of genes in the most prominent VH family (VH ...[more]

PMID: 24409278

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Dataset Information

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

Background/objective

Design

Methods

Results

Conclusions

Publications

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

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