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Macrophage-activating-factors (MAFs) alter HIV-1 production from primary mononuclear phagocytes.




 

Int Conf AIDS. 1989 Jun 4-9;5:525 (abstract no. W.C.O.8). Unique

Infection of mononuclear phagocytes by HIV-1 is believed to be a central event in the pathogenesis of AIDS. It is not clear, however, whether activating signals alter HIV production from these key target cells. We have studied the effects of several MAFs, including recombinant tumor necrosis factor-alpha (rTNF), interferon-gamma (rIFNg) and lipopolysaccharide (LPS), on HIV-1 production from blood monocyte-derived macrophages (MDM). MDM were purified (greater than 99% esterase +) from normal donors by density-gradient centrifugation and adherence to plastic in 10% human serum. After 1-2 weeks of culture, MDM were infected with HIV-1 (strain HTLV-IIIB) at a multiplicity of infection of approximately 5. Virus production was determined by ELISA of culture supernatants and cell lysates for HIV p24 antigen. Treatment of MDM with rTNF (10(2)-10(3) U/ml), starting either 2 days before or 7 days after HIV-1 infection, increased virus production 5-fold over control. Treatment with LPS (1-10 ng/ml) starting 7 days after infection increased virus production 4-10 fold over control. In contrast, rIFNg (1-10(3) U/ml) inhibited HIV-1 replication (38-95% inhibition). Viral inhibition was observed irrespective of the timing of rIFNg treatment in relation to HIV-1 infection. Similar inhibition was produced by recombinant interferon-alpha(2a) or native interferon-beta, indicating that anti-HIV activity was not specific for rIFNg. These studies indicate that interferons inhibit HIV-1 replication in MDM, but that rTNF and LPS enhance virus production from these cells. These observations, combined with clinical evidence that T-cell IFNg production declines and circulating TNF levels rise with progression of HIV-1 infection to AIDS, suggest that certain MAFs may be important modulators of HIV-1 replication in vivo.

HIV Infections/*MICROBIOLOGY HIV-1/DRUG EFFECTS/*GROWTH & DEVELOPMENT Interferon Type II/PHARMACOLOGY Lipopolysaccharides *Macrophage Activation Phagocytes/*MICROBIOLOGY Tumor Necrosis Factor/PHARMACOLOGY *Virus Replication ABSTRACT



 




Information in this article was accurate in September 30, 1990. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.