title: The toll-like receptor 3-mediated antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice.
abstract: RIG-I-like receptors and Toll-like receptors (TLRs) play important roles in the recognition of viral infections. However, how these molecules contribute to the defense against poliovirus (PV) infection remains unclear. We characterized the roles of these sensors in PV infection in transgenic mice expressing the PV receptor. We observed that alpha/beta interferon (IFN-α/β) production in response to PV infection occurred in an MDA5-dependent but RIG-I-independent manner in primary cultured kidney cells in vitro. These results suggest that, similar to the RNA of other picornaviruses, PV RNA is recognized by MDA5. However, serum IFN-α levels, the viral load in nonneural tissues, and mortality rates did not differ significantly between MDA5-deficient mice and wild-type mice. In contrast, we observed that serum IFN production was abrogated and that the viral load in nonneural tissues and mortality rates were both markedly higher in TIR domain-containing adaptor-inducing IFN-β (TRIF)-deficient and TLR3-deficient mice than in wild-type mice. The mortality rate of MyD88-deficient mice was slightly higher than that of wild-type mice. These results suggest that multiple pathways are involved in the antiviral response in mice and that the TLR3-TRIF-mediated signaling pathway plays an essential role in the antiviral response against PV infection.
authors.affiliation: Neurovirology Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Abe
authors.forename: Ken
authors.initials: K
authors.lastname: Fujii
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oshiumi
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koike
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D000818:Animals; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011051:Poliomyelitis / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D017955:Poliovirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011991:Receptors, Virus / Q000235:genetics* / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D007370:Interferon Type I; D011991:Receptors, Virus; D051196:Toll-Like Receptor 3; C476286:Ticam1 protein, mouse; C066100:poliovirus receptor
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