AEGiS-11IAC: HIV-1 replication in epithelial intestinal cells.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

HIV-1 replication in epithelial intestinal cells.

Int Conf AIDS 1996 Jul 7-12; 11:217 (abstract no. Tu.A.142)
Chenine AL, Sanchez G, LeContel C, Godard C, Chermann JC, Hirsch I; INSERM, Unite de Recherches sur les Retrovirus et Maladies Associees, Marseille, France. Fax: (33) 91 41 92 50.

OBJECTIVE: The human colon epithelial line HT29 was used as a model for study of persistent and abortive infection with HIV-1 in CD4 negative cells.

METHODS: Infection of HT29 cells with different subtypes of HIV-1 was followed by production of reverse transcriptase activity or p24gag to cell free supernatant or by cocultivation with MT4 lymphocytes.

RESULTS: At least thousand HT29 cells had to be infected with HIV-1 NDK, a clade D Zairian virus highly cytopathic for CD4 positive lymphocytes, to establish a massive and persistent virus production in a total population of 106 intestinal cells. Bellow this critical proportion, the HIV-1 NDK infected cells were progressively aborted from the culture, like in the case of the prototype clade B virus HIV-1 LAV. Infection with primary clinical isolates of subtypes A, B, C, D, E and F was also abortive. Low production (less than or equal to 102 TCIU/ml), characteristic for a period of several weeks after infection of HT29 cells with HIV-1 NDK produced in CEM lymphocytes (HIV-1 NDKCEM), was followed by an adaptation and massive virus production (106 TCIU/ml). The adapted HIV-1 NDKHT29 virus was about hundred times and ten thousands times more infectious for HT29 cells than HIV-1 NDKCEM and HIV-1 LAV, respectively. After adaptation, HIV-1 NDKHT29 was produced and its DNA was detected in about 10% of HT29 cells whereas the rest of cells was free of the virus or its DNA. HIV-1 NDKHT29 producing cell clones derived from persistently infected culture divided about 50% slowier than non-infected cells. Infection of intestinal cells with HIV-1 NDK is not followed by cytopathic changes visible by optical microscopy. Their cocultivation with macrophages, but not with lymphocytes, infected with macrophage-tropic virus HIV-1 PAR resulted in drastic changes in their growth properties and morphology.

CONCLUSIONS: Our results indicate that difference between persistent and abortive infection depends on dynamic equilibrium of (i) kinetics of HIV-1 production, (ii) its infectivity for intestinal cells, (iii) reduced growth rate of infected cells related to their negative selection and (iv) overgrowth by uninfected cells.

Keywords: AEGIS, HIV-1, Virus Replication, RNA-Directed DNA Polymerase, HIV Core Protein p24, Antigens, CD4, HIV Antibodies, HIV Infections, HIV Envelope Protein gp120, HIV, CD4-Positive T-Lymphocytes, Epithelial Cells, Macrophages, HIV Seropositivity, Lymphocytes, Human, virology, ICA11

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TuA142