Suppression of NF-κB and AP-1 activation in monocytic cells persistently infected with measles virus

Abstract: A major cause of the high morbidity and mortality associated with measles infection is attributed to virus-mediated immunosuppression. In this report, we present evidence for a novel strategy of immunosuppression by the measles virus. We observed a marked suppression of lipopolysaccharide (LPS)-induced IL-8, RANTES, TNF-α and IL-6 production and NF-κB activation in human monocytic cell lines persistently infected with measles virus. This effect was not observed in human epithelial cells lines persistently infected with measles virus. There were no significant differences in expression levels of Toll-like receptors (TLRs) and their associated molecules, or other intracellular signaling molecules of the NF-κB signaling pathway in measles-virus-infected monocytic cells compared to uninfected cells. Infected monocytic cells exhibited decreased LPS-induced DNA binding of NF-κB and phosphorylation of JNK, namely activation of transcription factors NF-κB and AP-1. NF-κB was constitutively activated in human epithelial cells persistently infected with measles virus, and LPS treatment resulted in further activation. The cell-type-specific suppression of NF-κB activation represents a potential strategy of escape from the host immune system by measles virus via induced immunological silencing in infected cells. [Copyright &y& Elsevier]