MACROPHAGE-TROPIC AND T-CELL LINE-ADAPTED CHIMERIC STRAINS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DIFFER IN THEIR SUSCEPTIBILITIES TO NEUTRALIZATION BY SOLUBLE CD4 AT DIFFERENT TEMPERATURES

Molecular clones of three macrophage-tropic and three T-cell line-adap ted strains of human immunodeficiency virus type 1 (HIV-1) were used t o explore the mechanism of HIV-1 resistance to neutralization by solub le CD4 (sCD4). The three macrophage-tropic viruses, each possessing th e V3 and flanking regions of JR-FL, were all resistant to sCD4 neutral ization under the standard conditions of a short preincubation of the virus and sCD4 at 37 degrees C prior to inoculation of peripheral bloo d mononuclear cells. In contrast, the three T-cell line-adapted viruse s, NL4-3 and two chimeras possessing the V3 and flanking regions of NL 4-3 in the envelope background of JR-FL, were all sCD4 sensitive under these conditions. Sensitivity to sCD4 neutralization at 37 degrees C corresponded with rapid, sCD4-induced gp120 shedding from the viruses. However, when the incubation temperature of the sCD4 and virus was re duced to 4 degrees C, the three macrophage-tropic viruses shed gp120 a nd became more sensitive to sCD4 neutralization. In contrast, the rate s of sCD4 induced gp120 shedding and virus neutralization were reduced for the three T-cell line-adapted viruses at 4 degrees C. Thus, HIV r esistance to sCD4 is a conditional phenomenon; macrophage-tropic and T -cell line-adapted strains can be distinguished by the temperature dep endencies of their neutralization by sCD4. The average density of gp12 0 molecules on the macrophage-tropic viruses exceeded by about fourfol d that on the T-cell line-adapted viruses, suggesting that HIV growth in T-cell lines may select for a destabilized envelope glycoprotein co mplex. Further studies of early events in HIV-1 infection should focus on primary virus strains.