MACROPHAGE AND T-CELL LINE TROPISMS OF HIV-1 ARE DETERMINED BY SPECIFIC REGIONS OF THE ENVELOPE GP120 GENE

Strains of human immunodeficiency virus type 1 (HIV-1) display a high degree of biological heterogeneity which may be linked to certain clinical manifestations 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 at a specific region of the envelope gp120 gene representing 159 amino-acid residues of glycoprotein gp 120 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.