Hoffmann Federico G, He Xiang, West John T, Lemey Philippe, Kankasa Chipepo, Wood Charles
School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588-0666, USA.
AIDS. 2008 Apr 23;22(7):817-24. doi: 10.1097/QAD.0b013e3282f486af.
To characterize the envelope (Env) glycoprotein of HIV-1 in mother-infant pairs (MIP) that underwent near simultaneous or acute-phase seroconversion, we examined the Env sequence of the transmitted viruses and compare viral evolution within the pair.
Three MIP from a Zambian cohort that seroconverted at the same sampling time were identified and followed longitudinally.
The V1-V5 region of the HIV-1 Env gene was sequenced for each sample collected. Phylogenetic and population genetics analyses were carried out to subtype the viruses, estimate relationships among viral genotypes, and compare molecular evolution between the viral populations.
Genetic analyses demonstrated a close intrapair relationship between viral sequences from each MIP. Transmission involved several closely related viral genotypes and did not result in a reduction in viral diversity. Amino acid changes were not evenly distributed along Env V1-V5 but concentrated in concordant areas within each MIP. Several positions under positive selection were shared between the MIP viruses. Interestingly, selective pressure on the virus was higher in the infants than in the mothers.
In contrast to most cases of perinatal transmission of HIV-1 from chronically infected mothers, there is no evidence of a genetic bottleneck in the transmitted viruses in these three instances of acute seroconversion. The longitudinal changes in the amino acids are in similar positions in Env for the MIP, suggesting shared evolutionary constrains among the closely related viruses infecting the MIP; such constrains may lead to similar genetic changes in the virus in two different hosts.
为了对经历了近乎同时或急性期血清转化的母婴对(MIP)中HIV-1的包膜(Env)糖蛋白进行特征分析,我们检测了传播病毒的Env序列,并比较了母婴对中病毒的进化情况。
从赞比亚队列中鉴定出在同一采样时间发生血清转化的三对母婴,并进行纵向跟踪。
对收集的每个样本的HIV-1 Env基因的V1-V5区域进行测序。进行系统发育和群体遗传学分析,以对病毒进行亚型分类,估计病毒基因型之间的关系,并比较病毒群体之间的分子进化。
遗传分析表明,每对母婴的病毒序列之间存在密切的配对内关系。传播涉及几种密切相关的病毒基因型,并未导致病毒多样性降低。氨基酸变化并非沿Env V1-V5均匀分布,而是集中在每对母婴的一致区域。几对母婴的病毒之间共享了几个正选择位点。有趣的是,婴儿体内病毒的选择压力高于母亲。
与大多数慢性感染母亲围产期传播HIV-1的情况不同,在这三例急性血清转化中,没有证据表明传播的病毒存在基因瓶颈。母婴对Env中氨基酸的纵向变化处于相似位置,表明感染母婴对的密切相关病毒之间存在共同的进化限制;这种限制可能导致两种不同宿主中的病毒发生相似的基因变化。