Human immunodeficiency virus can infect the apical and basolateral surfaces of human colonic epithelial cells.
The gastrointestinal tract is considered to be a major route of infection for the human immunodeficiency virus (HIV). To understand the interaction of HIV with epithelial cells of the intestinal mucosa, we have studied the infection of a human colon cancer cell clone HT-29-D4. The enterocyte-like differentiation of this clone can be modulated in vitro according to the concentration of glucose. We show that: (i) undifferentiated HT-29-D4 cells can be infected by HIV types 1 and 2 (HIV-1 and HIV-2) strains with no subsequent effect on cell growth; (ii) undifferentiated HT-29-D4 cells express a CD4-related antigen bearing epitopes of the immunoglobulin-like variable (V) region domains V1 and V2 of CD4 but lacking the epitope known to be involved in HIV envelope recognition; (iii) differentiated HT-29-D4 cells can be infected by HIV after an interaction with either the apical brush border membrane (luminal side) or the basolateral side (serosal side); (iv) the CD4-like molecule is restricted to the basolateral domain of differentiated cells; and (v) the infection is not inhibited by anti-CD4 monoclonal antibodies (mAbs) OKT4, OKT4A, Leu-3a, Bl4, 13-B-8-2, S-T4 or S-T40. We conclude that epithelial intestinal cells may represent a major site of entry for HIV. Infection of these epithelial cells may occur via the basolateral membrane by HIV-bearing lymphocytes or macrophages of the lamina propria and via the apical membrane by HIV present in the bowel lumen. This infection may remain silent for up to 9 months, and the virus can be rescued by cocultivation with lymphoid cells. These data may give an explanation for the long latent seronegative state that may occur in a HIV-infected individual.
Fantini
J
J
Institut National de la Santé et de la Recherche Médicale, Unité 322, Unit of Retrovirus and Associated Diseases, Marseille, France.
Yahi
N
N
Chermann
J C
JC
D000230:Adenocarcinoma; D015704:CD4 Antigens; D002460:Cell Line; D002472:Cell Transformation, Viral; D003110:Colonic Neoplasms; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004848:Epithelium / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D015498:HIV-2 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism
D015704:CD4 Antigens; D004279:DNA, Viral; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase