Changes in Growth Properties on Passage in Tissue Culture of Viruses Derived from Infectious Molecular Clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI

The construction and preliminary biological characterization of three molecular clones of human immunodeficiency virus type 1 (HIV-1) are reported: HIV-1LAI from a French man with AIDS, HIV-1MAL from a Zairian boy with ARC, and HIV-1ELI from a Zairian woman with AIDS. All three sequences were found to code for infectious viruses. Both the host range and the kinetics of infection in CD4+ cells were different for the three viruses. Virus derived from each molecular clone was infectious on peripheral blood mononuclear cells (PBMC), although LAI and ELI displayed more rapid growth kinetics than MAL. The viruses had different tropisms and growth kinetics in six cell lines. LAI was infectious in all of the cell lines and produced high levels of reverse transcriptase activity. MAL and ELI had more restricted tropisms: MAL could only replicate on SupT1, whereas ELI grew on Jurkat and MT-4, was delayed on CEM and H9, and was unable to infect U937 cells. In addition, we observed that both the replicative capacity and the cell tropism of viruses could change after passage through some established cell lines. These results suggest that the genotypes of some viruses in vitro are not stable and that selection for growth can cause the fairly rapid appearance of variants with increased growth potential.