Zhang L Q, MacKenzie P, Cleland A, Holmes E C, Brown A J, Simmonds P
Centre for HIV Research, University of Edinburgh, Edinburgh, United Kingdom.
J Virol. 1993 Jun;67(6):3345-56. doi: 10.1128/JVI.67.6.3345-3356.1993.
Viral RNA was extracted from plasma samples collected from five individuals during the period of viremia before seroconversion in primary infection with human immunodeficiency virus type 1 (HIV-1) and amplified by polymerase chain reaction. Nucleotide sequence analysis of amplified DNA from the V3 and V4 hypervariable regions indicated that the initial virus population of each acutely infected individual was completely homogeneous in sequence. No intrasample variability was found among the 44,090 nucleotides sequenced in this region of env, contrasting with the high degree of variability normally found in seropositive individuals. Paradoxically, substantial sequence variability was found in the normally high conserved gag gene (encoding p17) in most of the preseroconversion samples. The diversity of p17 sequences in samples that were homogeneous in V3 and V4 can most readily be explained by the existence of strong selection for specific env sequences either upon transmission or in the interval between exposure and seroconversion in the exposed individual. Evidence that localizes the selected region upon transmission to V3 is provided by the similarity or identity of V3 loop sequences in five individuals with epidemiologically unrelated HIV-1 infections, while regions flanking the V3 loop and the V4 hypervariable region were highly divergent. The actual V3 sequences were similar to those associated with macrophage tropism in primary isolates of HIV, irrespective of whether infection was acquired by sexual contact or parenterally through transfusion of contaminated factor VIII. Proviral DNA sequences in peripheral blood mononuclear cells remained homogeneous in the V3 and V4 regions (and variable in p17gag) for several months after seroconversion. The persistence of HIV sequences in peripheral blood mononuclear cells identical to those found at primary infection in the absence of continued virus expression provides an explanation for the previously observed differences in the composition of circulating DNA and RNA populations in sequential samples from seropositive individuals.
从5名个体在1型人类免疫缺陷病毒（HIV-1）原发性感染血清转化前病毒血症期间采集的血浆样本中提取病毒RNA，并通过聚合酶链反应进行扩增。对V3和V4高变区扩增DNA的核苷酸序列分析表明，每个急性感染个体的初始病毒群体在序列上完全相同。在env基因的该区域测序的44,090个核苷酸中未发现样本内变异性，这与血清阳性个体中通常发现的高度变异性形成对比。矛盾的是，在大多数血清转化前样本中，通常高度保守的gag基因（编码p17）中发现了大量序列变异性。V3和V4区域相同的样本中p17序列的多样性最容易通过在传播时或暴露个体暴露与血清转化之间的间隔中对特定env序列存在强烈选择来解释。在5名患有流行病学上无关的HIV-1感染的个体中，V3环序列的相似性或同一性提供了将传播时选定区域定位到V3的证据，而V3环两侧的区域和V4高变区高度不同。实际的V3序列与HIV原发性分离株中与巨噬细胞嗜性相关的序列相似，无论感染是通过性接触还是通过输注受污染的凝血因子VIII经肠道外获得。血清转化后几个月，外周血单核细胞中的前病毒DNA序列在V3和V4区域保持相同（而p17gag可变）。在没有持续病毒表达的情况下，外周血单核细胞中与原发性感染时发现的HIV序列相同的持续存在，为先前观察到的血清阳性个体连续样本中循环DNA和RNA群体组成差异提供了解释。
