1. Elevated hypermutation levels in HIV-1 natural viral suppressors.
- Author
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Eyzaguirre LM, Charurat M, Redfield RR, Blattner WA, Carr JK, and Sajadi MM
- Subjects
- Antiretroviral Therapy, Highly Active, DNA, Viral analysis, DNA, Viral genetics, DNA, Viral isolation & purification, Female, Genome, Viral genetics, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, HIV-1 physiology, Humans, Leukocytes, Mononuclear virology, Male, Molecular Sequence Data, Phylogeny, Proviruses genetics, Sequence Analysis, DNA, HIV-1 genetics, HIV-1 pathogenicity, Mutation, Virus Inactivation
- Abstract
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 NVS patients had defective proviral genomes, compared to 4 of the treated controls (40%, p = 0.96) and only one of the untreated controls (8%, p = 0.059). Most of the defective genomes resulted from Gto-A hypermutation. Among patients with hypermutation, the rate ratio for mutation was significantly higher for the NVS compared to treated controls (p = 0.043). Our data suggests that inactivation of the virus through the APOBEC3G system may contribute to the NVS phenotype., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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