Human herpesvirus 6 infection impairs Toll-like receptor signaling | Murakami et al. Virology Journal 2010 7 91 http content 7 1 91 VIROLOGY JOURNAL SHORT REPORT Open Access Human herpesvirus 6 infection impairs Toll-like receptor signaling Yuichi Murakami 1 Kazushi Tanimoto1 Hiroshi Fujiwara1 2 Jun An1 Koichiro Suemori1 Toshiki Ochi1 Hitoshi Hasegawa1 2 and Masaki Yasukawa 1 2 Abstract Human herpesvirus 6 HHV-6 has a tropism for immunocompetent cells including T lymphocytes monocytes macrophages and dendritic cells DCs suggesting that HHV-6 infection affects the immunosurveillance system. Tolllike receptor TLR system plays an important role in innate immunity against various pathogens. In the present study we investigated the effect of HHV-6 infection on the expression and intracellular signaling of TLRs in DCs. Although expression levels of TLRs were not decreased or slightly elevated following HHV-6 infection the amounts of cytokines produced following stimulation with ligands for TLRs appeared to be dramatically decreased in HHV-6-infected DCs as compared to mock-infected DCs. Similarly phosphorylation levels of TAK-1 IkB kinase and lKB-a following stimulation of HHV-6-infected DCs with lipopolysaccharide which is the ligand for TLR4 appeared to be decreased. These data show that HHV-6 impairs intracellular signaling through TLRs indicating the novel mechanism of HHV-6-mediated immunomodulation. Findings Human herpesvirus 6 HHV-6 is known as a causative agent of exanthem subitum and reactivation of HHV-6 in adults causes various clinical manifestations 1 2 . HHV-6 can preferentially infect immunocompetent cells and induces various immunobiological alterations 3-12 . Therefore HHV-6 is recognized as one of the important viruses that modulate immune responses. Toll-like receptors TLRs are key molecules of the innate immune system 13 . A subset of TLRs recognizes components of microorganisms and induces innate immune responses. After recognition of ligands TLRs activate their intrinsic signaling pathways resulting
