title: A tryptophan-rich motif in the human parainfluenza virus type 2 V protein is critical for the blockade of toll-like receptor 7 (TLR7)- and TLR9-dependent signaling.
abstract: Plasmacytoid dendritic cells (pDCs) do not produce alpha interferon (IFN-α) unless viruses cause a systemic infection or overcome the first-line defense provided by conventional DCs and macrophages. We show here that even paramyxoviruses, whose infections are restricted to the respiratory tract, have a V protein able to prevent Toll-like receptor 7 (TLR7)- and TLR9-dependent IFN-α induction specific to pDCs. Mutational analysis of human parainfluenza virus type 2 demonstrates that the second Trp residue of the Trp-rich motif (Trp-X(3)-Trp-X(9)-Trp) in the C-terminal domain unique to V, a determinant for IRF7 binding, is critical for the blockade of TLR7/9-dependent signaling.
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Mayu
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Takayuki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Machiko
authors.initials: M
authors.lastname: Nishio
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Masae
authors.initials: M
authors.lastname: Itoh
authors.forename: Bin
authors.initials: B
authors.lastname: Gotoh
mesh_terms: D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D010223:Parainfluenza Virus 2, Human / Q000472:pathogenicity*; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors*; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C068854:V protein, human parainfluenza virus type 1; D014764:Viral Proteins