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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, View ORCID ProfileMariano A. Garcia-Blanco
doi: https://doi.org/10.1101/2020.03.24.005900
K. Reddisiva Prasanth
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
Minato Hirano
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
W. Samuel Fagg
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
2Transplant Division, Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA
Eileen T. McAnarney
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
Chao Shan
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
Xuping Xie
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
Adam Hage
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
Colette A. Pietzsch
4Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA
5Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA
Alexander Bukreyev
4Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA
5Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA
Ricardo Rajsbaum
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
6Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA
Pei-Yong Shi
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
6Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA
Mark T. Bedford
7Department of Epigenetics and Molecular Carcinogenesis, MD Anderson Cancer Center, Smithville, Texas, USA
Shelton S. Bradrick
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
6Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA
Vineet Menachery
3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
Mariano A. Garcia-Blanco
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
6Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA
8Programme 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.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Posted March 27, 2020.
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
bioRxiv 2020.03.24.005900; doi: https://doi.org/10.1101/2020.03.24.005900
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
bioRxiv 2020.03.24.005900; doi: https://doi.org/10.1101/2020.03.24.005900
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