Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication-Reference-Cited by-同舟云学术

Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication

Published:2023-02-10 Issue:6632 Volume:379 Page:586-591
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Tsukamoto Yuta¹^ORCID,Hiono Takahiro²³^ORCID,Yamada Shintaro¹^ORCID,Matsuno Keita²⁴⁵^ORCID,Faist Aileen⁶⁷^ORCID,Claff Tobias⁸^ORCID,Hou Jianyu⁸^ORCID,Namasivayam Vigneshwaran⁸^ORCID,vom Hemdt Anja⁹^ORCID,Sugimoto Satoko¹⁰,Ng Jin Ying¹^ORCID,Christensen Maria H.¹¹^ORCID,Tesfamariam Yonas M.¹¹^ORCID,Wolter Steven¹²,Juranek Stefan¹³,Zillinger Thomas¹²¹⁴¹⁵^ORCID,Bauer Stefan¹⁴^ORCID,Hirokawa Takatsugu¹⁶¹⁷¹⁸^ORCID,Schmidt Florian I.¹¹¹⁹^ORCID,Kochs Georg²⁰²¹^ORCID,Shimojima Masayuki¹⁰,Huang Yi-Shuian²²²³^ORCID,Pichlmair Andreas²⁴²⁵^ORCID,Kümmerer Beate M.⁹²⁶^ORCID,Sakoda Yoshihiro²³^ORCID,Schlee Martin¹²^ORCID,Brunotte Linda⁶²⁷,Müller Christa E.⁸^ORCID,Igarashi Manabu²²⁸^ORCID,Kato Hiroki¹^ORCID

Affiliation:

1. Institute of Cardiovascular Immunology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.

2. International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.

3. Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

4. Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.

5. One Health Research Center, Hokkaido University, Sapporo, Hokkaido, Japan.

6. Institute of Virology Muenster, Westfaelische Wilhelms–University, Muenster, Germany.

7. CiM-IMPRS, Westfaelische Wilhelms–University Muenster, International Max Planck Research School – Molecular Biomedicine, Muenster, Germany.

8. PharmaCenter Bonn and Pharmaceutical Institute, Pharmaceutical and Medicinal Chemistry, University of Bonn, Bonn, Germany.

9. Institute of Virology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.

10. Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.

11. Institute of Innate Immunity, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.

12. Institute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty, University Hospital Bonn, Bonn, Germany.

13. Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, University of Bonn, Bonn, Germany.

14. Institute of Immunology, Philipps–University Marburg, Marburg, Germany.

15. Department of Biomedicine, Aarhus University, Aarhus, Denmark.

16. Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan.

17. Division of Biomedical Science, University of Tsukuba, Tsukuba, Japan.

18. Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.

19. Core Facility Nanobodies, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.

20. Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.

21. Faculty of Medicine, University of Freiburg, Freiburg, Germany.

22. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

23. Neuroscience Program of Academia Sinica, Academia Sinica, Taipei, Taiwan.

24. Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany.

25. German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany.

26. German Center for Infection Research (DZIF), partner site Bonn-Cologne, Bonn, Germany.

27. Interdisciplinary Center for Medical Research, Medical Faculty Muenster, Germany.

28. Division of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.

Abstract

Orthomyxo- and bunyaviruses steal the 5′ cap portion of host RNAs to prime their own transcription in a process called “cap snatching.” We report that RNA modification of the cap portion by host 2′-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from Streptomyces , called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its S -adenosyl- l -methionine binding pocket to restrict influenza virus replication. Mechanistically, TFMT impairs the association of host cap RNAs with the viral polymerase basic protein 2 subunit in human lung explants and in vivo in mice. TFMT acts synergistically with approved anti-influenza drugs.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.add0875

Reference37 articles.

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4. Sequestration by IFIT1 Impairs Translation of 2′O-unmethylated Capped RNA

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