Topoisomerase III-ß 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:10.1101/2020.03.24.005900

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

bioRxiv [Preprint]. 2020 Mar 27:2020.03.24.005900. doi: 10.1101/2020.03.24.005900.

Authors

K Reddisiva Prasanth¹, Minato Hirano¹, W Samuel Fagg^{1

2}, Eileen T McAnarney³, Chao Shan¹, Xuping Xie¹, Adam Hage³, Colette A Pietzsch^{4

5}, Alexander Bukreyev^{4

5}, Ricardo Rajsbaum^{3

6}, Pei-Yong Shi^{1

6}, Mark T Bedford⁷, Shelton S Bradrick^{1

6}, Vineet Menachery³, Mariano A Garcia-Blanco^{1

6

8}

Affiliations

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

Abstract

Based on genome-scale loss-of-function screens we discovered that Topoisomerase III-ß (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.

Publication types

Preprint