Shioda T, Levy J A, Cheng-Mayer C
Department of Medicine, University of California, San Francisco 94143-0128.
Nature. 1991 Jan 10;349(6305):167-9. doi: 10.1038/349167a0.
Strains of human immunodeficiency virus type 1 (HIV-1) display a high degree of biological heterogeneity which may be linked to certain clinical manifestation of AIDS. They vary in their ability to infect different cell types, to replicate rapidly and to high titre in culture, to down-modulate the CD4 receptor, and to cause cytopathic changes in infected cells. Some of these in vitro properties correlate with pathogenicity of the virus in vivo. To map the viral determinants of the cellular host range of HIV-1, recombinant viruses were generated between biologically active molecular clones of HIV-1 isolates showing differences in infection of primary peripheral blood macrophages and established T-cell lines. We report here that a specific region of the envelope gp120 gene representing 159 amino-acid residues of glycoprotein gp120 seems to determine macrophage tropism, whereas an overlapping region representing 321 amino-acid residues determines T cell-line tropism. These studies provide a basis for relating functional domains of the HIV-1 env gene to pathogenic potential.
1型人类免疫缺陷病毒(HIV-1)毒株表现出高度的生物学异质性,这可能与艾滋病的某些临床表现有关。它们在感染不同细胞类型、在培养中快速复制并达到高滴度、下调CD4受体以及在受感染细胞中引起细胞病变变化的能力方面存在差异。其中一些体外特性与病毒在体内的致病性相关。为了绘制HIV-1细胞宿主范围的病毒决定因素,在HIV-1分离株的生物活性分子克隆之间产生了重组病毒,这些分离株在原发性外周血巨噬细胞和已建立的T细胞系感染方面存在差异。我们在此报告,包膜糖蛋白gp120基因的一个特定区域,代表糖蛋白gp120的159个氨基酸残基,似乎决定了巨噬细胞嗜性,而一个代表321个氨基酸残基的重叠区域决定了T细胞系嗜性。这些研究为将HIV-1 env基因的功能域与致病潜力联系起来提供了基础。