The monocyte/macrophage (M/M) system represents an important target of HIV infection. Unlike infection of CD4+ T cells, infection of M/Ms results in persistent, low level expression of HIV rather than cell lysis. A number of cytokines have been shown to influence human immunodeficiency virus (HIV) infection. Recently, the beta chemokines RANTES, MIP-1alpha and MIP-1beta were shown to be capable of suppressing certain HIV strains in T cells. In order to investigate the mechanism whereby HIV infection is controlled in the M/M system, the role of the cytokine network, especially beta chemokines, in HIV infection was studied in primary monocyte-derived macrophages (MDM) as well as promonocytic U937 subclones. We demonstrated that: (1) CD8+ T-cell culture supernatants could, but beta chemokines could not, suppress HIV-1 macrophage-tropic Ba-L replication in MDM; (2) antibodies to beta chemokines could not reduce the ability of the CD8+ T-cell culture supernatants to inhibit HIV-1 Ba-L infection in the M/M system while antibodies to intereleukin (IL)-10, IL-13, interferon (IFN)-alpha, and IFN-gamma in combination partially neutralized this activity; and (3) the CD8+ T-cell culture supernatants could, but beta chemokines could not, suppress replication of the T-cell tropic strain HIV-IIIB in peripheral blood mononuclear cells and HIV expression from chronically HIV-infected U1 cells. These results suggest that the anti-HIV activity of CD8+ T cells is a multifactorial phenomenon, and that CD8+ T cells produce soluble factor(s) other than RANTES, MIP-1alpha, and MIP-1beta that suppress replication of various HIV-1 strains in both lymphocytes and M/M systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000741-01
Application #
2441371
Study Section
Special Emphasis Panel (LIR)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Suthar, Mehul S; Gale Jr, Michael; Owen, David M (2009) Evasion and disruption of innate immune signalling by hepatitis C and West Nile viruses. Cell Microbiol 11:880-8
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O'Hara, Andrea J; Chugh, Pauline; Wang, Ling et al. (2009) Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma. PLoS Pathog 5:e1000389