Respiratory syncytial virus G-protein modulates cytokine release from human peripheral blood mononuclear cells

Abstract

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in children and adults. In vivo the host has to cope with intact replicative virus, with non-replicative virus, and/or with viral structural proteins including the outer membrane G-protein. We analyzed the role of purified RSV G-protein with regard to its modulatory efficacy for interleukin (IL) -10, IL-12, and tumor necrosis factor-alpha (TNF-alpha) release from human peripheral blood mononuclear cells (PBMC). These cytokines seem to contribute to the deleterious effect in viral infections. Treatment of PBMC with RSV at a multiplicity of infection of 10 down to 0.001 induced the release of TNF-alpha, IL-10, and IL-12; also time kinetics and dose-responses differed markedly. Stimulation of PBMC with purified RSV G-protein (from 0.001 up to 10 microgram/10(6) PBMC) led only to a pronounced increase in IL-10 within a concentration range from 0.01 up to 0.5 microgram/10(6) PBMC with a maximum between 12 and 18 h of incubation. AT later time points (24, 48, and 72 h) G-protein concentrations above 1 microgram/10(6) PBMC suppressed IL-10, TNF-alpha, and IL-12 release from human PBMC. Coating of PBMC with RSV G-protein suppressed IL-10, TNF-alpha, and IL-12 release after subsequent stimulation with RSV. Our data indicate a regulatory role of RSV G-protein immune responses toward viral infection.