Burger H, Weiser B, Flaherty K, Gulla J, Nguyen P N, Gibbs R A
Department of Medicine, State University of New York, Stony Brook 11794.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11236-40. doi: 10.1073/pnas.88.24.11236.
The degree of change in the nucleotide sequence of human immunodeficiency virus type 1 (HIV-1) that occurs when it is transmitted sexually from one individual to another or vertically from mother to child is unknown. Previous studies have shown that most cultured HIV-1 isolates from the same individuals differed in the entire envelope gene nucleotide sequence by up to 2%, although most isolates from unrelated individuals differed by 6-22%. To examine diversity among HIV-1 isolates from close contacts, we determined the nucleotide sequences of viruses from a family with a known epidemiologic profile, in which a woman transmitted HIV-1 heterosexually to her partner and vertically to her daughter. Direct DNA sequence analysis of primary HIV-1 isolates amplified by PCR was used to distinguish the major and minor viral sequences, termed quasispecies, to rapidly determine the predominant sequences and their phylogenetic relationships. The nucleotide sequence diversity of a major portion of the HIV-1 envelope gene was 3.7% between isolates from the woman and her heterosexual partner and 8.5% between isolates from this woman and her daughter, who had been infected for a longer period than the partner. The configuration of the phylogenetic tree demonstrated that the daughter's predominant isolate evolved from a progenitor of her mother's current strain. This study provides evidence of a continuous spectrum of sequence diversity between any two isolates ranging from those derived from the same person to those from close contacts and, ultimately, those from unrelated individuals. These data and methods can be applied to epidemiologic investigations of possible HIV-1 transmission between health care workers and their patients.
人类免疫缺陷病毒1型（HIV-1）在个体间性传播或母婴垂直传播时发生的核苷酸序列变化程度尚不清楚。先前的研究表明，来自同一人的大多数培养HIV-1分离株在整个包膜基因核苷酸序列上的差异高达2%，而来自无关个体的大多数分离株差异为6%-22%。为了研究来自密切接触者的HIV-1分离株之间的多样性，我们测定了一个具有已知流行病学特征的家庭中病毒的核苷酸序列，在这个家庭中，一名女性将HIV-1通过异性传播给她的伴侣，并垂直传播给她的女儿。通过PCR扩增的原始HIV-1分离株的直接DNA序列分析用于区分主要和次要病毒序列，即准种，以快速确定主要序列及其系统发育关系。该女性与其异性伴侣的分离株之间HIV-1包膜基因大部分区域的核苷酸序列多样性为3.7%，该女性与其感染时间比伴侣更长的女儿的分离株之间为8.5%。系统发育树的构型表明，女儿的主要分离株是从她母亲当前菌株的祖先进化而来的。这项研究提供了证据，证明从同一人衍生的分离株到密切接触者的分离株，最终到无关个体的分离株，任意两个分离株之间存在连续的序列多样性谱。这些数据和方法可应用于医护人员及其患者之间可能的HIV-1传播的流行病学调查。
