Laboratorio de Biología Celular y Retrovirus - CONICET, Hospital de Pediatría Juan P. Garrahan, Ciudad de Buenos Aires, Argentina.
Infect Genet Evol. 2011 Aug;11(6):1256-62. doi: 10.1016/j.meegid.2011.04.020. Epub 2011 May 5.
The APOBEC3G protein is a restriction factor that can inhibit the replication of HIV-1. The virus has the capacity to counteract this antiviral activity through the expression of the Vif accessory protein, which recruits a CUL5-based ubiquitin ligase complex that determines APOBEC3G proteasomal degradation. In this work we evaluated in a large pediatric cohort (i) whether single nucleotide polymorphisms of APOBEC3G and CUL5 genes (APOBEC3G H186R, APOBEC3G C40693T and CUL5 SNP6) can alter the risk of HIV-1 vertical transmission and/or the rate of progression to AIDS, (ii) the effect of HIV-1 Vif variants on the clinical course of disease, and (iii) whether the patient genotype for the studied polymorphisms could have an impact on Vif characteristics. We found no effect of the studied APOBEC3G or CUL5 genetic variants on vertical transmission or progression to pediatric AIDS. However, we detected an association of certain Vif alterations (a one amino acid insertion at position 61 and the substitutions A62D/N/S and Q136P) with an accelerated AIDS outcome. Additionally, we observed that the APOBEC3G C40693T and CUL5 SNP6 minor alleles were correlated with substitutions in Vif motifs that are involved in the interaction with APOBEC3G and CUL5 proteins, respectively. Our results suggest that Vif alterations may contribute to a rapid AIDS onset and that Vif variability could be influenced by APOBEC3G and CUL5 polymorphisms in children.
APOBEC3G 蛋白是一种限制因子，可以抑制 HIV-1 的复制。病毒有能力通过表达 Vif 辅助蛋白来对抗这种抗病毒活性，该蛋白招募了一个基于 CUL5 的泛素连接酶复合物，该复合物决定了 APOBEC3G 的蛋白酶体降解。在这项工作中，我们在一个大型儿科队列中评估了（i）APOBEC3G 和 CUL5 基因的单核苷酸多态性（APOBEC3G H186R、APOBEC3G C40693T 和 CUL5 SNP6）是否可以改变 HIV-1 垂直传播的风险和/或进展为艾滋病的速度，（ii）HIV-1 Vif 变体对疾病临床过程的影响，以及（iii）研究的多态性患者基因型是否会对 Vif 特征产生影响。我们没有发现研究的 APOBEC3G 或 CUL5 遗传变异对垂直传播或儿科艾滋病进展的影响。然而，我们检测到某些 Vif 改变（第 61 位的一个氨基酸插入以及 A62D/N/S 和 Q136P 的取代）与艾滋病加速发生有关。此外，我们观察到 APOBEC3G C40693T 和 CUL5 SNP6 较小等位基因与参与与 APOBEC3G 和 CUL5 蛋白相互作用的 Vif 基序的取代相关。我们的结果表明，Vif 改变可能导致艾滋病的快速发作，并且 Vif 的变异性可能受到儿童中 APOBEC3G 和 CUL5 多态性的影响。
