title: The herpes simplex virus 1-encoded envelope glycoprotein B activates NF-κB through the Toll-like receptor 2 and MyD88/TRAF6-dependent signaling pathway.
abstract: The innate immune response plays a critical role in the host defense against invading pathogens, and TLR2, a member of the Toll-like receptor (TLR) family, has been implicated in the immune response and initiation of inflammatory cytokine secretion against several human viruses. Previous studies have demonstrated that infectious and ultraviolet-inactivated herpes simplex virus 1 (HSV-1) virions lead to the activation of nuclear factor kappa B (NF-κB) and secretion of proinflammatory cytokines via TLR2. However, except for the envelope glycoprotein gH and gL, whether there are other determinants of HSV-1 responsible for TLR2 mediated biological effects is not known yet. Here, we demonstrated that the HSV-1-encoded envelope glycoprotein gB displays as molecular target recognized by TLR2. gB coimmunoprecipitated with TLR2, TLR1 and TLR6 in transfected and infected human embryonic kidney (HEK) 293T cells. Treatment of TLR2-transfected HEK293T (HEK293T-TLR2) cells with purified gB results in the activation of NF-κB reporter, and this activation requires the recruitment of the adaptor molecules myeloid differentiation primary-response protein 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) but not CD14. Furthermore, activation of NF-κB was abrogated by anti-gB and anti-TLR2 blocking antibodies. In addition, the expression of interleukin-8 induced by gB was abrogated by the treatment of the human monocytic cell line THP-1 with anti-TLR2 blocking antibody or by the incubation of gB with anti-gB antibody. Taken together, these results indicate the importance and potency of HSV-1 gB as one of pathogen-associated molecular patterns (PAMPs) molecule recognized by TLR2 with immediate kinetics.
authors: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors: Mingsheng
authors: M
authors: Cai
authors: Meili
authors: M
authors: Li
authors: Kezhen
authors: K
authors: Wang
authors: Shuai
authors: S
authors: Wang
authors: Qiong
authors: Q
authors: Lu
authors: Jinghua
authors: J
authors: Yan
authors: Karen L
authors: KL
authors: Mossman
authors: Rongtuan
authors: R
authors: Lin
authors: Chunfu
authors: C
authors: Zheng
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins; D015398:Signal Transduction; D012995:Solubility; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011994:Recombinant Proteins; D048029:TNF Receptor-Associated Factor 6; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D014759:Viral Envelope Proteins
references: Nature. 1996 Oct 3;383(6599):443-6
references: 8837778
references: Cell Microbiol. 2004 May;6(5):401-10
references: 15056211
references: J Biol Chem. 1999 Nov 19;274(47):33419-25
references: 10559223
references: Eur J Immunol. 2005 Mar;35(3):911-21
references: 15714590
references: J Virol. 2004 Aug;78(15):7867-73
references: 15254159
references: Immunol Lett. 2002 Nov 1;84(2):89-95
references: 12270544
references: Nat Rev Immunol. 2004 Jul;4(7):499-511
references: 15229469
references: J Immunol. 2005 Sep 1;175(5):3165-76
references: 16116207
references: Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11335-9
references: 18682563
references: Curr Opin Immunol. 2003 Aug;15(4):396-401
references: 12900270
references: Infect Immun. 2001 Aug;69(8):4951-7
references: 11447173
references: J Clin Invest. 2001 Jan;107(1):13-9
references: 11134172
references: J Immunol. 2000 Jul 15;165(2):618-22
references: 10878331
references: J Immunol. 2002 Feb 15;168(4):1533-7
references: 11823477
references: Annu Rev Cell Dev Biol. 1996;12:627-61
references: 8970739
references: Nat Immunol. 2001 Aug;2(8):675-80
references: 11477402
references: Eur J Immunol. 2005 Jan;35(1):282-9
references: 15580661
references: Nat Immunol. 2005 Jun;6(6):565-70
references: 15895089
references: PLoS One. 2010 Oct 29;5(10):e13742
references: 21060793
references: Nat Struct Mol Biol. 2010 Oct;17(10):1266-8
references: 20852645
references: Scand J Infect Dis. 2003;35(9):555-62
references: 14620134
references: J Virol. 2005 Oct;79(20):12658-66
references: 16188968
references: J Virol. 2011 May;85(10):5003-15
references: 21389132
references: Gastroenterology. 2004 Nov;127(5):1513-24
references: 15521019
references: J Clin Invest. 1985 Jan;75(1):226-33
references: 3880773
references: Virology. 1998 Nov 25;251(2):317-26
references: 9837796
references: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1315-20
references: 14739339
references: J Virol. 1998 Mar;72(3):1826-33
references: 9499033
references: Annu Rev Immunol. 2006;24:353-89
references: 16551253
references: Cell. 2008 Mar 21;132(6):935-44
references: 18358807
references: J Virol. 2008 Nov;82(21):10493-501
references: 18715929
references: J Immunol. 2005 Oct 1;175(7):4189-93
references: 16177057
references: Viral Immunol. 2005;18(2):267-81
references: 16035939
references: J Virol. 1989 Jan;63(1):52-8
references: 2535752
references: J Clin Invest. 2001 Aug;108(4):503-10
references: 11518721
references: J Virol. 2002 Sep;76(17):8820-33
references: 12163602
references: Arch Virol. 2011 Dec;156(12):2267-72
references: 21894520
references: J Virol. 2011 Feb;85(4):1881-6
references: 21147926
references: J Virol. 2003 Apr;77(8):4588-96
references: 12663765
references: Nature. 2002 Nov 21;420(6913):329-33
references: 12447442
references: Nature. 2010 Oct 14;467(7317):859-62
references: 20944748
references: Infect Dis Clin North Am. 1999 Jun;13(2):341-53, vii
references: 10340170
references: Am J Pathol. 2005 May;166(5):1419-26
references: 15855642
references: J Virol. 2012 Jun;86(12):6555-62
references: 22496225
references: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17343-8
references: 17085599
references: J Virol. 2002 Sep;76(17):8729-36
references: 12163593
references: J Immunol. 2001 Jan 1;166(1):15-9
references: 11123271
references: J Immunol. 2006 Nov 15;177(10):7094-102
references: 17082626
references: J Immunol. 2009 Jan 15;182(2):851-9
references: 19124728
references: J Exp Med. 1998 Dec 7;188(11):2091-7
references: 9841923