Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, Oxford University, South Parks Road, Oxford, OX1 3SY, UK.
Retrovirology. 2011 Jul 7;8:54. doi: 10.1186/1742-4690-8-54.
To combat the pandemic of human immunodeficiency virus 1 (HIV-1), a successful vaccine will need to cope with the variability of transmissible viruses. Human hosts infected with HIV-1 potentially harbour many viral variants but very little is known about viruses that are likely to be transmitted, or even if there are viral characteristics that predict enhanced transmission in vivo. We show for the first time that genetic divergence consistent with a single transmission event in vivo can represent several years of pre-transmission evolution.
We describe a highly unusual case consistent with a single donor transmitting highly related but distinct HIV-1 variants to two individuals on the same evening. We confirm that the clustering of viral genetic sequences, present within each recipient, is consistent with the history of a single donor across the viral env, gag and pol genes by maximum likelihood and bayesian Markov Chain Monte Carlo based phylogenetic analyses. Based on an uncorrelated, lognormal relaxed clock of env gene evolution calibrated with other datasets, the time since the most recent common ancestor is estimated as 2.86 years prior to transmission (95% confidence interval 1.28 to 4.54 years).
Our results show that an effective design for a preventative vaccine will need to anticipate extensive HIV-1 diversity within an individual donor as well as diversity at the population level.
为了应对人类免疫缺陷病毒 1（HIV-1）的流行，成功的疫苗将需要应对可传播病毒的变异性。感染 HIV-1 的人类宿主可能携带许多病毒变异体，但对于可能传播的病毒知之甚少，甚至不知道是否存在预测体内增强传播的病毒特征。我们首次表明，与体内单次传播事件一致的遗传差异可能代表了几年的前传播进化。
我们描述了一个非常不寻常的情况，一个单一的供体在同一个晚上向两个个体传播了高度相关但不同的 HIV-1 变体。我们通过最大似然和基于贝叶斯马尔可夫链蒙特卡罗的系统发育分析证实，每个受体内存在的病毒遗传序列聚类与跨越病毒 env、gag 和 pol 基因的单一供体的历史一致。基于 env 基因进化的无关联、对数正态松弛时钟与其他数据集进行校准，估计从最近共同祖先到传播的时间为 2.86 年前（95%置信区间为 1.28 至 4.54 年）。
我们的研究结果表明，预防性疫苗的有效设计需要预测个体供体内部以及人群水平的广泛 HIV-1 多样性。
