Sato H, Shiino T, Kodaka N, Taniguchi K, Tomita Y, Kato K, Miyakuni T, Takebe Y
Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo 162-8640, Japan.
J Virol. 1999 May;73(5):3551-9. doi: 10.1128/JVI.73.5.3551-3559.1999.
It has been suggested that immune-pressure-mediated positive selection operates to maintain the antigenic polymorphism on the third variable (V3) loop of the gp120 of human immunodeficiency virus type 1 (HIV-1). Here we present evidence, on the basis of sequencing 147 independently cloned env C2/V3 segments from a single family (father, mother, and their child), that the intensity of positive selection is related to the V3 lineage. Phylogenetic analysis and amino acid comparison of env C2/V3 and gag p17/24 regions indicated that a single HIV-1 subtype E source had infected the family. The analyses of unique env C2/V3 clones revealed that two V3 lineage groups had evolved in the parents. Group 1 was maintained with low variation in all three family members regardless of the clinical state or the length of infection, whereas group 2 was only present in symptomatic individuals and was more positively charged and diverse than group 1. Only virus isolates carrying the group 2 V3 sequences infected and induced syncytia in MT2 cells, a transformed CD4(+)-T-cell line. A statistically significant excess of nonsynonymous substitutions versus synonymous substitutions was demonstrated only for the group 2 V3 region. The data suggest that HIV-1 variants, possessing the more homogeneous group 1 V3 element and exhibiting the non-syncytium-inducing phenotype, persist in infected individuals independent of clinical status and appear to be more resistant to positive selection pressure.
有人提出，免疫压力介导的正向选择作用于维持人类免疫缺陷病毒1型（HIV-1）gp120第三可变区（V3）环上的抗原多态性。在此，我们基于对来自一个家庭（父亲、母亲及其孩子）的147个独立克隆的env C2/V3片段进行测序，提供证据表明正向选择的强度与V3谱系有关。env C2/V3和gag p17/24区域的系统发育分析和氨基酸比较表明，单一的HIV-1 E亚型毒株感染了该家庭。对独特的env C2/V3克隆的分析显示，父母体内已进化出两个V3谱系组。第1组在所有三名家庭成员中变异程度较低，无论临床状态或感染时长如何；而第2组仅出现在有症状的个体中，且比第1组带正电荷更多、多样性更高。只有携带第2组V3序列的病毒分离株能感染MT2细胞（一种转化的CD4(+) T细胞系）并诱导其形成多核巨细胞。仅在第2组V3区域观察到非同义替换相对于同义替换有统计学意义的过量。数据表明，具有更均一的第1组V3元件且表现出非诱导多核巨细胞形成表型的HIV-1变体，在感染个体中持续存在，与临床状态无关，且似乎对正向选择压力更具抗性。
