Ulenga Nzovu K, Sarr Abdoulaye Dieng, Hamel Donald, Sankale Jean-Louis, Mboup Souleymane, Kanki Phyllis J
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
AIDS Res Hum Retroviruses. 2008 Oct;24(10):1285-90. doi: 10.1089/aid.2008.0072.
The APOBEC family of mammalian cytidine deaminases, such as APOBEC3G (hA3G), has been demonstrated to function as a host viral restriction factor against HIV-1. hA3G has been shown to cause extensive G-to-A mutations in the HIV-1 genome, which may play a role in viral restriction. To investigate the role of G-to-A mutations in HIV-1 pathogenesis, we isolated, amplified, and sequenced HIV-1 sequences (vif, gag, and env) from 29 therapy-naive HIV-1-infected individuals. The levels of G-to-A mutations correlated with the expression levels of hA3G in the vif (rho = 0.438, p = 0.041) and the env regions (rho = 0.392, p = 0.038), but not in the gag region (rho = 0.131, p = 0.582). There is no correlation between viral load and the level of G-to-A mutations in the vif (rho = 0.144, p = 0.522), env (rho = 0.168, p = 0.391), or gag regions (rho = -0.254, p = 0.279). Taken together, these findings suggest that the hA3G-induced G-to-A mutations may not be the mechanism by which hA3G restricts or controls viral replication. Thus, hA3G might be restricting viral growth in infected individuals through a mechanism that is independent of the cytidine deaminase activities of hA3G.
哺乳动物胞苷脱氨酶的载脂蛋白B mRNA编辑酶催化多肽样（APOBEC）家族，如载脂蛋白B mRNA编辑酶催化多肽样3G（hA3G），已被证明可作为宿主针对HIV-1的病毒限制因子发挥作用。hA3G已被证明会在HIV-1基因组中导致广泛的G到A突变，这可能在病毒限制中发挥作用。为了研究G到A突变在HIV-1发病机制中的作用，我们从29名未经治疗的HIV-1感染个体中分离、扩增并测序了HIV-1序列（vif、gag和env）。G到A突变的水平与vif区域（rho = 0.438，p = 0.041）和env区域（rho = 0.392，p = 0.038）中hA3G的表达水平相关，但与gag区域（rho = 0.131，p = 0.582）无关。病毒载量与vif（rho = 0.144，p = 0.522）、env（rho = 0.168，p = 0.391）或gag区域（rho = -0.254，p = 0.279）中G到A突变的水平之间没有相关性。综上所述，这些发现表明hA3G诱导的G到A突变可能不是hA3G限制或控制病毒复制的机制。因此，hA3G可能通过一种独立于hA3G胞苷脱氨酶活性的机制来限制感染个体中的病毒生长。
