AEGiS-14IAC: Innate immunity in HIV infection: Importance of the interferon-producing cells.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Innate immunity in HIV infection: Importance of the interferon-producing cells.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1136)

Levy JA
University of California, San Francisco, San Francisco, United States

BACKGROUND: As the principle producers of IFN-a/b, the plasmacytoid interferon-producing cell (IPC) plays a pivotal role in both innate and adaptive immune responses. We have recently described a decline in circulating IPC numbers correlates with increased HIV plasma viral load and AIDS defining disease. Present studies were directed at understanding the consequences of the interactions between HIV and IPCs.

METHODS: IPCs express CD4 and both CCR5 and CXCR4. Purified IPCs (>99.5%) were exposed to SI or NSI isolates and stimulated by soluble CD40L. Cultures were observed for viability and HIV production in the presence or absence of activated CD4+ T cells. The ability of HIV to elicit IFN-a production was tested by exposing enriched IPCs (90-97%) to high titered virus or infected CD4+ T cells.

RESULTS: Viral replication in IPC cultures either with or without maturation by soluble CD40L was minimal. Further there was no loss of viability in HIV exposed IPCs . Virus was readily recovered after the addition of CD4+ T cells to the cultures, up to 7 days post-exposure. Transfer of virus was independent of DC-SIGN. Exposure of IPCs to HIV did not stimulate IFN-a production, nor did HIV inhibit HSV-stimulated IFN-a production. HIV infected T cells however are potent inducers of IFN-a production. HIV-1 SI and NSI and HIV-2 infected cells all induce IFN-a release.

CONCLUSIONS: We suggest that the decline in circulating IPCs is not due to their direct elimination by virus. However these cells can be infected with HIV. While IPCs are not major producers of HIV, they could be important reservoirs for HIV and can transfer virus to CD4+ T cells. The specific stimulation of IFN-a release by productively infected CD4+ T cells, not free virus, suggests IPCs could be important in controlling HIV replication in the lymph node. Treatments aimed at boosting IPC numbers may be effective in reducing HIV production and preventing opportunistic infections and cancer.

Keywords: AEGIS, HIV Infections, HIV-1, Immunity, Natural, Interferons, Antigens, CD4, Interferon-alpha, T-Lymphocytes, Virus Replication, CD40 Ligand, HIV-2, Acquired Immunodeficiency Syndrome, HIV Seropositivity, immunology, virology

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TuOrA1136