Evidence map›Paper›PMID 35590097›Full record

ArticleCommunications biology2022

SARS-CoV-2 ORF6 disrupts nucleocytoplasmic trafficking to advance viral replication.

Yoichi Miyamoto, Yumi Itoh, Tatsuya Suzuki, Tomohisa Tanaka, Yusuke Sakai, Masaru Koido, Chiaki Hata, Cai-Xia Wang, Mayumi Otani, Kohji Moriishi and 5 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Review
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  5. Review
  6. Article
  7. Human coronavirus 3CL protease manipulates host protein STIM1 to facilitate immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Molecular therapy. Nucleic acids · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 1 country.

Yoichi MiyamotoLaboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan. ymiyamoto@nibiohn.go.jp.ORCID 0000-0003-4016-1119
Yumi ItohInstitute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Tatsuya SuzukiInstitute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Tomohisa TanakaDepartment of Microbiology, Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.
Yusuke SakaiDepartment of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.ORCID 0000-0003-0531-8256
Masaru KoidoDepartment of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-0348-0666
Chiaki HataCell Engineering Corporation, Osaka, Japan.
Cai-Xia WangCell Engineering Corporation, Osaka, Japan.
Mayumi OtaniLaboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
Kohji MoriishiDepartment of Microbiology, Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.ORCID 0000-0002-9542-5188
Taro TachibanaCell Engineering Corporation, Osaka, Japan.
Yoichiro KamataniDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Yoshihiro YonedaNational Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
Toru OkamotoInstitute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. toru@biken.osaka-u.ac.jp.ORCID 0000-0003-4000-3102
Masahiro OkaLaboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.ORCID 0000-0003-0123-3060
National Institute of Biomedical Innovation, Health and Nutrition · JPThe University of Osaka · JPThe University of Tokyo · JPHokkaido University · JPNational Institute of Infectious Diseases · JPOsaka Metropolitan University · JPUniversity of Yamanashi · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 β1-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.

Indexed as

COVID-19SARS-CoV-2alpha KaryopherinsAnimalsAntiviral AgentsBiological TransportCricetinaeViral ProteinsVirus Replicationalpha KaryopherinsAntiviral AgentsORF6 protein, SARS-CoV-2Viral Proteins

Identifiers

PMID35590097
PMCPMC9120032
OpenAlexW4280575755

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.