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SARS-CoV-2 ORF6 disrupts nucleocytoplasmic trafficking to advance viral replication.
Miyamoto, Yoichi; Itoh, Yumi; Suzuki, Tatsuya; Tanaka, Tomohisa; Sakai, Yusuke; Koido, Masaru; Hata, Chiaki; Wang, Cai-Xia; Otani, Mayumi; Moriishi, Kohji; Tachibana, Taro; Kamatani, Yoichiro; Yoneda, Yoshihiro; Okamoto, Toru; Oka, Masahiro.
  • Miyamoto Y; Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan. ymiyamoto@nibiohn.go.jp.
  • Itoh Y; Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • Suzuki T; Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • Tanaka T; Department of Microbiology, Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.
  • Sakai Y; Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
  • Koido M; Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Hata C; Cell Engineering Corporation, Osaka, Japan.
  • Wang CX; Cell Engineering Corporation, Osaka, Japan.
  • Otani M; Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
  • Moriishi K; Department of Microbiology, Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.
  • Tachibana T; Division of Hepatitis Virology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
  • Kamatani Y; Cell Engineering Corporation, Osaka, Japan.
  • Yoneda Y; Department of Bioengineering, Graduate School of Engineering, Osaka Metropolitan University, Osaka, Japan.
  • Okamoto T; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
  • Oka M; National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
Commun Biol ; 5(1): 483, 2022 05 19.
Article in English | MEDLINE | ID: covidwho-1852521
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF6 is an antagonist of interferon (IFN)-mediated antiviral signaling, achieved through the prevention of STAT1 nuclear localization. However, the exact mechanism through which ORF6 prevents STAT1 nuclear trafficking remains unclear. Herein, we demonstrate that ORF6 directly binds to STAT1 with or without IFN stimulation, resulting in the nuclear exclusion of STAT1. ORF6 also recognizes importin α subtypes with different modes, in particular, high affinity to importin α1 but a low affinity to importin α5. Although ORF6 potentially disrupts the importin α/importin ß1-mediated nuclear transport, thereby suppressing the nuclear translocation of the other classical nuclear localization signal-containing cargo proteins, the inhibitory effect of ORF6 is modest when compared with that of STAT1. The results indicate that the drastic nuclear exclusion of STAT1 is attributed to the specific binding with ORF6, which is a distinct strategy for the importin α1-mediated pathway. Combined with the results from a newly-produced replicon system and a hamster model, we conclude that SARS-CoV-2 ORF6 acts as a virulence factor via regulation of nucleocytoplasmic trafficking to accelerate viral replication, resulting in disease progression.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Animals Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03427-4

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Animals Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03427-4