Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp!20 gene

Abstract

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^1–3, to replicate rapidly and to high titre in culture^4–6, to down-modulate the CD4 receptor^7,8, and to cause cytopathic changes in infected cells^7,9–11. Some of these in vitro properties correlate with pathogenicity of the virus in vivo^11,12. 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.