Infection of chimpanzee peripheral blood mononuclear cells by human immunodeficiency virus type 1 requires cooperative interaction between multiple variable regions of gp120

We have recently reported the isolation and molecular cloning of a human immunodeficiency virus type 1 isolate (HIV-1(DH125)) that exhibits rapid replication kinetics and marked cytopathicity in both human and chimpanzee peripheral blood mononuclear cells (PBMC). To identify the viral determinants responsible for infectivity of chimpanzee PBMC, chimeric viruses containing the following components were constructed: (i) the entire envelope gene; (ii) gp120 sequences; (iii) gp41 sequences; and (iv) individual or various combinations of the gp120 variable regions of HIV-1(DH125) inserted into the backbone of another HIV-1 isolate (HIV-1(AD8)), which is unable to infect chimpanzee PBMC. Analyses of virus replication kinetics in human and chimpanzee PBMC revealed that gp120 contains determinants which confer infectivity for chimpanzee PBMC and that the capacity to establish such an infection requires the cooperative interaction between multiple variable regions of the HIV-1(DH125) gp120.