Delwart E L, Shpaer E G, Louwagie J, McCutchan F E, Grez M, Rübsamen-Waigmann H, Mullins J I
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5402.
Science. 1993 Nov 19;262(5137):1257-61. doi: 10.1126/science.8235655.
The genetic diversity of human immunodeficiency virus (HIV) is a major concern thought to impact on immunologic escape and eventual vaccine efficacy. Here, simple and rapid methods are described for the detection and estimation of genetic divergence between HIV strains on the basis of the observation that DNA heteroduplexes formed between related sequences have a reduced mobility in polyacrylamide gels proportional to their degree of divergence. Reliable phylogenetic subtypes were assigned for HIV-1 strains from around the world. Relationships between viruses were closest when derived from the same or epidemiologically linked individuals. When derived from epidemiologically unlinked individuals, the relationships between viruses in a given geographic region correlated with the length of time HIV-1 had been detected in the population and the number of strains initiating widespread infection. Heteroduplex mobility analysis thus provides a tool to expedite epidemiological investigations by assisting in the classification of HIV and is readily applicable to the screening and characterization of other infectious agents and cellular genes.
人类免疫缺陷病毒(HIV)的基因多样性是一个主要问题,被认为会影响免疫逃逸及最终的疫苗效力。在此,基于相关序列之间形成的DNA异源双链体在聚丙烯酰胺凝胶中迁移率降低且与它们的差异程度成比例这一观察结果,描述了用于检测和估计HIV毒株之间基因差异的简单快速方法。为来自世界各地的HIV-1毒株指定了可靠的系统发育亚型。当病毒源自相同个体或有流行病学关联的个体时,它们之间的关系最为密切。当源自无流行病学关联的个体时,特定地理区域内病毒之间的关系与该人群中检测到HIV-1的时间长度以及引发广泛感染的毒株数量相关。因此,异源双链体迁移率分析提供了一种通过协助HIV分类来加速流行病学调查的工具,并且很容易应用于其他传染病原体和细胞基因的筛查与特征分析。