title: Human herpesvirus 6 infection impairs Toll-like receptor signaling.
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. Toll-like 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, IkappaB kinase, and IkappaB-alpha 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.
authors.affiliation: Departmemt of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Jun
authors.initials: J
authors.lastname: An
authors.forename: Koichiro
authors.initials: K
authors.lastname: Suemori
authors.forename: Toshiki
authors.initials: T
authors.lastname: Ochi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000821:virology*; D020869:Gene Expression Profiling; D015654:Herpesvirus 6, Human / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors
references.citation: Herpes. 2006 May;13(1):20-4
references.pmid: 16732999
references.citation: Trends Mol Med. 2007 Nov;13(11):460-9
references.pmid: 18029230
references.citation: J Immunol. 2001 Jan 15;166(2):1125-31
references.pmid: 11145693
references.citation: Annu Rev Immunol. 2003;21:335-76
references.pmid: 12524386
references.citation: Science. 1999 Apr 9;284(5412):309-13
references.pmid: 10195894
references.citation: J Virol. 1997 May;71(5):3751-9
references.pmid: 9094650
references.citation: Nature. 1997 Aug 7;388(6642):548-54
references.pmid: 9252186
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3094-9
references.pmid: 18287053
references.citation: Blood. 2003 Oct 15;102(8):2877-84
references.pmid: 12829600
references.citation: J Virol. 2002 Oct;76(20):10338-45
references.pmid: 12239310
references.citation: PLoS Pathog. 2008 Feb 8;4(2):e22
references.pmid: 18266467
references.citation: J Immunol. 1994 Jun 15;152(12):5768-75
references.pmid: 7911490
references.citation: Science. 1988 Oct 28;242(4878):540-6
references.pmid: 3140380
references.citation: Virology. 2009 Mar 15;385(2):294-302
references.pmid: 19144370
references.citation: Nat Rev Immunol. 2007 Mar;7(3):179-90
references.pmid: 17318230
references.citation: J Immunol. 1999 May 1;162(9):5417-22
references.pmid: 10228019
references.citation: Exp Hematol. 2006 May;34(5):642-53
references.pmid: 16647570
references.citation: Science. 1997 Oct 31;278(5339):860-6
references.pmid: 9346484
references.citation: J Exp Med. 2001 Sep 17;194(6):863-9
references.pmid: 11561001
references.citation: J Immunol. 1991 Jul 15;147(2):685-91
references.pmid: 1677024
references.citation: Cell. 1997 Oct 17;91(2):243-52
references.pmid: 9346241
references.citation: Nature. 1991 Feb 7;349(6309):533-5
references.pmid: 1846951
references.citation: Clin Microbiol Rev. 2005 Jan;18(1):217-45
references.pmid: 15653828
references.citation: Nature. 1993 Apr 1;362(6419):458-62
references.pmid: 7681936
references.citation: J Gen Virol. 2004 Sep;85(Pt 9):2639-2642
references.pmid: 15302957