title: Toll-like receptor 2 senses hepatitis C virus core protein but not infectious viral particles.
abstract: Toll-like receptors (TLRs) are pathogen recognition molecules activating the innate immune system. Cell surface expressed TLRs, such as TLR2 and TLR4, have been shown to play an important role in human host defenses against viruses through sensing of viral structural proteins. In this study, we aimed to elucidate whether TLR2 and TLR4 participate in inducing antiviral immunity against hepatitis C virus (HCV) by sensing viral structural proteins. We studied TLR2 and TLR4 activation by cell culture-derived infectious virions and serum-derived virions in comparison to purified recombinant HCV structural proteins and enveloped virus-like particles. Incubation of TLR2 or TLR4 transfected cell lines with recombinant core protein resulted in activation of TLR2-dependent signaling. In contrast, neither infectious virions nor enveloped HCV-like particles triggered TLR2 and TLR4 signaling. These findings suggest that monomeric HCV core protein but not intact infectious particles are sensed by TLR2. Impairment of interaction between TLR and the core in infectious viral particles may contribute to escape from innate antiviral immune responses.
authors.affiliation: Department of Medicine II, University of Freiburg, Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Jilg
authors.forename: Glaucia
authors.initials: G
authors.lastname: Paranhos-Baccalà
authors.forename: Françoise
authors.initials: F
authors.lastname: Stoll-Keller
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Peter
authors.initials: P
authors.lastname: Hafkemeyer
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: Heidi
authors.initials: H
authors.lastname: Barth
authors.forename: Philipp
authors.initials: P
authors.lastname: Henneke
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D016174:Hepacivirus / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014758:Viral Core Proteins