Elevated hypermutation levels in HIV-1 natural viral suppressors

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• 作者：Lindsay M. Eyzaguirre ; Manhattan Charurat ; Robert R. Redfield ; William A. Blattner ; Jean K. Carr ; Mohammad M. Sajadi
• 关键词：HIV-1 ; Natural viral suppressors (NVS) ; Hypermutation ; Elite controllers
• 刊名：Virology
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：443
• 期：2
• 页码：306-312
• 全文大小：1623 K

文摘

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.