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

Among host factors required for diverse groups of RNA viruses are components of the translation machinery and the proteasome, in addition to factors that mediate membrane transactions required for entry and exit of viruses. The understanding of the broad requirement for TOP3B among (+) ss RNA viruses will likely provide important insights into heretofore understudied steps in their lifecycles. While a requirement for human topoisomerase TOP1 in exacerbated inflammation induced by RNA virus infection has been previously documented 10 , the direct action of an RNA topoisomerase in viral replication is unprecedented, and has important biological implications. A requirement for a RNA topoisomerase as a critical cofactor for (+) ss RNA viruses is reasonable since viral genomes, because of their complex structures and size, especially the large coronaviruses, may lend themselves to topological problems (knots and catenanes) 11,12 . In parallel work focused on exploring these implications we have shown that TOP3B is required for a late step in DENV-2 replication, likely during the assembly of the genome into virions (Prasanth et al., manuscript in preparation). Furthermore, this action requires the topoisomerase activity of TOP3B since it is abrogated by a tyrosine to phenylalanine mutation (Y336F) in the active site of the enzyme (Ibid). The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.005900 doi: bioRxiv preprint