| Literature DB >> 28213497 |
Tatsuya Kozaki1,2,3, Jun Komano4, Daiki Kanbayashi5, Michihiro Takahama1,2,3, Takuma Misawa2,3, Takashi Satoh2,3, Osamu Takeuchi6, Taro Kawai7, Shigeomi Shimizu8, Yoshiharu Matsuura9, Shizuo Akira10,3, Tatsuya Saitoh11,2,3.
Abstract
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation. TIPARP typically localizes in the nucleus, but it accumulates in the cytoplasm after SINV infection, allowing targeting of cytoplasmic SINV RNA. Redistribution of TIPARP is induced by reactive oxygen species (ROS)-dependent oxidization of the nuclear pore that affects cytoplasmic-nuclear transport. BCL2-associated X protein (BAX) and BCL2 antagonist/killer 1 (BAK1), B-cell leukemia/lymphoma 2 (BCL2) family members, mediate mitochondrial damage to generate ROS after SINV infection. Thus, TIPARP is a viral RNA-sensing PRR that mediates antiviral responses triggered by BAX- and BAK1-dependent mitochondrial damage.Entities:
Keywords: RNA degradation; antiviral response; innate immunity; mitochondrial damage; reactive oxygen species
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Year: 2017 PMID： 28213497 PMCID： PMC5347618 DOI： 10.1073/pnas.1621508114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205