Murine cytomegalovirus infection inhibits tumor necrosis factor alpha responses in primary macrophages.
Despite robust host immune responses the betaherpesvirus murine cytomegalovirus (MCMV) is able to establish lifelong infection. This capacity is due at least in part to the virus utilizing multiple immune evasion mechanisms to blunt host responses. Macrophages are an important cell for MCMV infection, dissemination, and latency despite expression in the host of multiple cytokines, including tumor necrosis factor alpha (TNF-alpha), that can induce an antiviral state in macrophages or other cells. In this study, we found that MCMV infection of bone marrow-derived macrophages inhibited TNF-alpha-induced ICAM-1 surface expression and mRNA expression in infected cells via expression of immediate early and/or early viral genes. MCMV infection blocked TNF-alpha-induced nuclear translocation of NF-kappaB. This inhibition of TNF-alpha signaling was explained by a decrease in TNF receptor 1 (TNFR1) and TNFR2 that was due to decreased mRNA for the latter. These findings provide a mechanism by which MCMV can evade the effects of an important host cytokine in macrophages.
Popkin
Daniel L
DL
Department of Pathology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
Virgin
Herbert W
HW
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D051379:Mice; D018146:Muromegalovirus / Q000472:pathogenicity*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D047990:TNF Receptor-Associated Factor 1; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D015703:Antigens, CD; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D047990:TNF Receptor-Associated Factor 1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1