Lipopolysaccharide inhibits the production of lymphocytic choriomeningitis virus in a human monocytic cell line.
The human monocytic cell line THP-1 was used as a model to study the mechanism of infection in the monocyte/macrophage, a natural target of lymphocytic choriomeningitis virus (LCMV) infection in vivo. Both the virulent strain, LCMV.WE, and the avirulent strain, LCMV.ARM, infected THP-1 cells, but did not stimulate THP-1 cells to secrete interleukin 1 (IL-1) or tumour necrosis factor (TNF-alpha). When lipopolysaccharide (LPS) was added to THP-1 cells together with LCMV, an 80 to 90% reduction in the number of infected cells (measured by immunofluorescence) and a 90% reduction in viral plaques was observed 5 to 6 days post-infection. Neither interferon alpha (IFN-alpha) nor IFN-beta were detected in supernatants from THP-1 cells after the addition of LCMV, LPS, or LPS plus LCMV. In contrast, the same levels of IL-1 and TNF-alpha were observed in the presence of LPS and LCMV, or LPS alone. However, antibodies to IL-1, TNF-alpha, interleukin 6 and IFN-alpha did not block the antiviral effect of LPS. In kinetic studies, LPS added 1 day after adding LCMV to THP-1 cells was still effective in reducing the number of infected cells. Our findings suggest that LPS alters cellular metabolism, possibly through the induction of IFN-alpha, and that IFN-alpha in the absence of LPS suppresses virus production.
Krakauer
T
T
Disease Assessment Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011.
Peters
C J
CJ
D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000276:immunology*; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D016898:Interferon-alpha; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta