Interleukin-18 enhances HIV-1 production in a human chronically-infected T cell line (H9-V).
Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine expressed by activated macrophages, that induces production of interferon-gamma (IFN-gamma) and Th-1 development. Recently some investigators reported controversial in vitro data on IL-18 stimulation of HIV-1 replication in several cell lines. In the present study the effect of IL-18 on HIV replication in a human chronically HIV-1-infected lymphocytic T cell line (H9-V) was investigated. HIV-1 replication was determined by an immunoassay method in order to evaluate the content of p24 antigen in the cell culture supernatants. Stimulation of H9-V cells with IL-18 resulted in increased production of p24, especially at concentrations of 0.01 microg ml(-1) and 0.10 microg ml(-1). Moreover a significant and persistent IL-18 stimulation of HIV-1 replication was observed at a concentration of 0.01 microg ml(-1) during a 7-day period. Pre-treatment of IL-18 with a specific neutralizing monoclonal antibody significantly reduced HIV-1 replication. These experiments show that IL-18 promotes the increase of HIV-1 replication in human chronically-infected lymphocytic T cells and confirm the role of IL-18 as a proimflammatory cytokine in stimulating and maintaining HIV-1 replication during the course of the disease. In a successive set of experiments, since one of the main activities of IL-18 is the induction of IFN-gamma, we evaluated the effect of this biological modifier on H9-V cells. In particular, IFN-gamma shows a significant effect on cell replication and on reduction of CD4 and CD71 surface expression.
Pugliese
Agostino
A
Department of Medical and Surgical Sciences, Section of Clinical Microbiology, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164-20249 Turin, Italy. pugliese@dealer.it
Gennero
Luisa
L
Vidotto
Valerio
V
Speranza
Filippo
F
Tambini
Roberto
R
Torre
Donato
D
D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000494:pharmacology*; D011990:Receptors, Transferrin; D013601:T-Lymphocytes / Q000821:virology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D015704:CD4 Antigens; C068126:CD71 antigen; D016655:HIV Core Protein p24; D020382:Interleukin-18; D011990:Receptors, Transferrin; D007371:Interferon-gamma