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 cellular 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 prototype virus HIV-1 LAV was nonproductive. Recombinant viruses derived from HIV-1 LAV and HIV-1 NDK were used to determine the genetic control, step of virus/cell cycle, and molecular mechanism responsible for productive versus nonproductive infection of intestinal cells. Both parental viruses and all recombinants retrotranscribed their genomes with a similar kinetics and were able to complete HIV-1 DNA synthesis, HIV-1 LAV provirus present in preintegration complexes could be rescued by cocultivation with T-lymphocytes. However, it was aborted during prolonged cultivation of HT29 cells. Our results suggest that (i) gag/pol region of HIV-1 genome (fragment BssHII255-EcoRI4183) genetically controlled productive infection of intestinal cells and that (ii) the difference between productive and abortive infection occurred before synthesis of HIV-1 mRNA, at the integration level.
De Mareuil
J
J
INSERM U322, Unité de Recherches sur les Rétrovirus et Maladies Associées, Parc Scientifique et Technologique de Luminy, Marseille, France.
Guettari
N
N
Bolmont
C
C
Salaun
D
D
Baillon
J G
JG
Hostomsky
Z
Z
Hirsch
I
I
D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000821:virology*; D004279:DNA, Viral / Q000096:biosynthesis; D015683:Gene Products, gag / Q000235:genetics; D015750:Genes, gag / Q000235:genetics*; D015751:Genes, pol / Q000235:genetics*; D016679:Genome, Viral; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016914:Ribonuclease H / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*; D054301:gag Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C061169:p18 gag protein, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016914:Ribonuclease H