Topoisomerase III-β is required for efficient replication of positive-sense RNA viruses

K Reddisiva Prasanth; Minato Hirano; W Samuel Fagg; Eileen T McAnarney; Chao Shan; Xuping Xie; Adam Hage; Colette A Pietzsch; Alexander Bukreyev; Ricardo Rajsbaum; Pei-Yong Shi; Mark T Bedford; Shelton S Bradrick; Vineet Menachery; Mariano A Garcia-Blanco

doi:10.1016/j.antiviral.2020.104874

Topoisomerase III-β is required for efficient replication of positive-sense RNA viruses

Antiviral Res. 2020 Oct:182:104874. doi: 10.1016/j.antiviral.2020.104874. Epub 2020 Jul 28.

Authors

Affiliations

¹ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
² Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Transplant Division, Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
³ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
⁴ Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.
⁵ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
⁶ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
⁷ Department of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Smithville, TX, USA.
⁸ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore. Electronic address: maragarc@utmb.edu.

Abstract

Based on genome-scale loss-of-function screens we discovered that Topoisomerase III-β (TOP3B), a human topoisomerase that acts on DNA and RNA, is required for yellow fever virus and dengue virus-2 replication. Remarkably, we found that TOP3B is required for efficient replication of all positive-sense-single stranded RNA viruses tested, including SARS-CoV-2. While there are no drugs that specifically inhibit this topoisomerase, we posit that TOP3B is an attractive anti-viral target.

Keywords: Dengue; Host factor; Positive stranded RNA viruses; SARS-CoV-2; Topoisomerase III-ß (TOP3B).

MeSH terms

Betacoronavirus / physiology*
Cell Line
DNA Topoisomerases, Type I / metabolism*
Dengue Virus / physiology
Ebolavirus / physiology
Gene Knockout Techniques
Humans
Influenza A virus / physiology
RNA Viruses / metabolism*
SARS-CoV-2
Virus Replication / physiology*
Yellow fever virus / physiology
Zika Virus / physiology

Substances

TOP3B protein, human
DNA Topoisomerases, Type I

Abstract

MeSH terms

Substances

Grants and funding