INCREASE IN SENSITIVITY TO SOLUBLE CD4 BY PRIMARY HIV TYPE-1 ISOLATESAFTER PASSAGE THROUGH C8166 CELLS - ASSOCIATION WITH SEQUENCE DIFFERENCES IN THE FIRST CONSTANT (C1) REGION OF GLYCOPROTEIN-120

Primary isolates of human immunodeficiency virus type 1 (HIV-1) were o btained by coculture of peripheral blood lymphocytes (PBLs) from HIV-1 -infected people with PBLs from uninfected donors, These viral stocks tend to be resistant to neutralization/inactivation by soluble CD4 (sC D4). When these stocks were passed through the T cell line C8166, viru s stocks emerged that were sensitive to sCD4, Pre- and post-CS166 stoc ks maintained their sCD4-resistant and -sensitive phenotypes, respecti vely, with further passage in PBLs, Pre- and post-C8166 stocks were bi ologically cloned by two cycles of limiting dilution, The majority (14 of 17) of pre-C8166 clones were sCD4 resistant, and, conversely, the majority of post-C8166 clones (11 of 12) were sensitive to sCD4. Nucle otide and predicted amino acid sequence analysis in the env (gp120) re gion revealed a limited number of differences between the clones, The only differences that sorted with biological phenotype were in the fir st constant (C1) region of gp120. Adaptation to growth in C8166 cells and conversion from the sCD4-resistant to the sCD4-sensitive phenotype represent the emergence to prominence of viral species in the pre-C81 66 stock that have a replication advantage in C8166 coincident with in creased sensitivity to sCD4.