RESTRICTION OF HIV-1 REPLICATION IN INTESTINAL-CELLS IS GENETICALLY CONTROLLED BY THE GAG-POL REGION OF THE HIV-1 GENOME

The human colon epithelial line HT29 represents a semipermisive cellul ar system for human immunodeficiency virus type 1 (HIV-1). It could be productively infected with HIV-1 NDK, a Zairian virus isolate highly cytopathic for CD4 positive lymphocytes, whereas infection with the pr ototype virus HIV-1 LAV was nonproductive. Recombinant viruses derived from HIV-1 LAV and HIV-1 NDK were used to determine the genetic contr ol, step of virus/cell cycle, and molecular mechanism responsible for productive versus nonproductive infection of intestinal cells. Both pa rental viruses and all recombinants retrotranscribed their genomes wit h a similar kinetics and were able to complete HIV-1 DNA synthesis. HI V-1 LAV provirus present in preintegration complexes could be rescued by cocultivation with T-lymphocytes. However, it was aborted during pr olonged cultivation of HT29 cells. Our results suggest that (i) gag/po l region of HIV-1 genome (fragment BssHII(255)- EcoRI(4183)) genetical ly controlled productive infection of intestinal cells and that (ii) t he difference between productive and abortive infection occurred befor e synthesis of HIV-1 mRNA, at the integration level. (C) 1995 academic Press, Inc.