RANTES and MCP-3 inhibit the replication of T-cell-tropic human immunodeficiency virus type 1 strains (SF-2, MN, and HE).
The effects of the C-C chemokines RANTES (regulation upon activation normal T-cell expressed and secreted) and MCP-3 (monocyte chemotactic protein 3) on human immunodeficiency virus (HIV) replication in normal human peripheral blood mononuclear cells (PBMC) activated in vitro with phytohemagglutinin (PHA) were investigated. The following T-cell line-tropic (T-tropic) HIV strains were tested: HIV type 1 (HIV-1) SF-2, HIV-1 IIIB, HIV-1 MN, HIV-1 NDK, HIV-1 HE, HIV-1 NL4-3, HIV-2 ROD, and HIV-2 EHO. The strain most sensitive to the antiviral effects of RANTES and MCP-3 appeared to be HIV-1 SF-2. A 50% inhibitory concentration for HIV-1 SF-2 of 4 ng of RANTES per ml was obtained, and that of MCP-3 was about 1 ng/ml. However, MCP-3 was inactive at 100 ng/ml. Other HIV-1 strains, such as MN and HE, were less sensitive to the antiviral effects of RANTES and MCP-3, whereas all the other HIV strains tested were insensitive. Although the ratio of CD3+ CD4+ to CD3+ CD8+ T cells was the same in HIV-infected PBMC cultures treated or untreated with the chemokines, RANTES and MCP-3 interfered with the binding of monoclonal antibody (MAb) OKT4 to the CD4 receptor on T cells but not with the binding of MAb OKT4A. Therefore, RANTES and MCP-3 not only interfere with the HIV-induced fusion process but also have some modulating effect on the CD4 cell receptor. The chemokines did not affect HIV-1 binding to PHA-stimulated PBMC. Taken together, our observations point to the important role that both RANTES and MCP-3 may play in inhibiting HIV-1 replication of certain T-tropic strains in primary PBMC cultures. This may have important implications for immunotherapeutic strategies designed to slow down disease progression in AIDS.
Schols
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Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. Dominique.Schols@rega.kuleuven.ac.be
Proost
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Van Damme
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De Clercq
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D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D015704:CD4 Antigens / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018946:Chemokine CCL5 / Q000494:pharmacology*; D054410:Chemokine CCL7; D016207:Cytokines; D005434:Flow Cytometry; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D015498:HIV-2 / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology*; D010835:Phytohemagglutinins; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C515450:CCL7 protein, human; D015704:CD4 Antigens; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D010835:Phytohemagglutinins