Elevated hypermutation levels in HIV-1 natural viral suppressors.
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ABSTRACT:
SUBMITTER: Eyzaguirre LM
PROVIDER: S-EPMC3762252 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Publications
Elevated hypermutation levels in HIV-1 natural viral suppressors.
Eyzaguirre Lindsay M LM Charurat Manhattan M Redfield Robert R RR Blattner William A WA Carr Jean K JK Sajadi Mohammad M MM
Virology 20130619 2
Mutations in the HIV-1 proviral genomes delay the progression of the disease. We compared the mutation status in full-length proviral genomes of 23 HIV-infected patients with undetectable viral loads in the absence of therapy named natural viral suppressors (NVS) or Elite Controllers with 23 HIV-infected controls (10 patients on HAART treatment and 13 untreated patients). Provirus DNA was extracted from PBMC for amplification and sequencing to determine the mutation status. Nine (39 %) of the 23 ...[more]
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Project description:ObjectiveIn this study, we aimed to investigate the frequency and activation of invariant natural killer T (iNKT) cells and natural killer (NK) cells among HIV-1, HIV-2, or dually HIV-1/HIV-2 (HIV-D)-infected individuals, in relation to markers of disease progression.DesignWhole blood samples were collected from treatment-naive HIV-1 (n = 23), HIV-2 (n = 34), and HIV-D (n = 11) infected individuals, as well as HIV-seronegative controls (n = 25), belonging to an occupational cohort in Guinea-Bissau.MethodsFrequencies and activation levels of iNKT and NK cell subsets were analysed using multicolour flow cytometry, and results were related to HIV-status, CD4 T-cell levels, viral load, and T-cell activation.ResultsHIV-1, HIV-D, and viremic HIV-2 individuals had lower numbers of CD4 iNKT cells in circulation compared with seronegative controls. Numbers of CD56 NK cells were also reduced in HIV-infected individuals as compared with control study participants. Notably, iNKT cell and NK cell activation levels, assessed by CD38 expression, were increased in HIV-1 and HIV-2 single, as well as dual, infections. HIV-2 viremia was associated with elevated activation levels in CD4 iNKT cells, CD56, and CD56 NK cells, as compared with aviremic HIV-2 infection. Additionally, disease markers such as CD4 T-cell percentages, viral load, and CD4 T-cell activation were associated with CD38 expression levels of both iNKT and NK cells, which activation levels also correlated with each other.ConclusionOur data indicate that elevated levels of iNKT-cell and NK-cell activation are associated with viremia and disease progression markers in both HIV-1 and HIV-2 infections.
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