Distler O, McQueen P W, Tsang M L, Evans L A, Hurren L, Byrne C, Penny R, Cooper D A, Delaney S F
Department of Biotechnology, University of New South Wales, Australia.
J Infect Dis. 1995 Nov;172(5):1384-7. doi: 10.1093/infdis/172.5.1384.
V3 loop sequences were compared from 5 human immunodeficiency virus type 1 (HIV-1)-infected patients over time. Three patients remained asymptomatic and 2 became symptomatic with large decrease in CD4 cell counts. The patient isolates were previously evaluated for phenotypic and antigenic properties and had different sensitivities to serum neutralization and changes in phenotype. This study showed a number of amino acid changes for the 2 symptomatic patients, each of whom progressed to AIDS during the study. The only amino acid substitution consistently associated with reduced CD4 cell counts, cytopathic effect, and progression to AIDS was Arg at position 11. Specific amino acid changes could not be correlated with increasing serum neutralization resistance or cytotropism changes. Increased loop charge was associated with a switch from macrophage to T cell tropism and a decrease in the number of CD4 cells. The study shows the importance of naturally occurring mutations in the V3 loop in controlling the biologic properties of HIV-1.
对5名1型人类免疫缺陷病毒(HIV-1)感染患者不同时间的V3环序列进行了比较。3名患者仍无症状,2名出现症状,CD4细胞计数大幅下降。这些患者分离株先前已进行表型和抗原特性评估,对血清中和作用及表型变化具有不同敏感性。本研究显示,2名有症状患者出现了一些氨基酸变化,这两名患者在研究期间均进展为艾滋病。唯一始终与CD4细胞计数减少、细胞病变效应及进展为艾滋病相关的氨基酸替换是第11位的精氨酸。特定的氨基酸变化与血清中和抗性增加或嗜亲性变化无关。环电荷增加与从巨噬细胞嗜亲性向T细胞嗜亲性转变以及CD4细胞数量减少有关。该研究表明V3环中自然发生的突变在控制HIV-1生物学特性方面的重要性。