The reovirus μ2 C-terminal loop inversely regulates NTPase and transcription functions versus binding to factory-forming μNS and promotes replication in tumorigenic cells.

ABSTRACT: Wild type reovirus serotype 3 'Dearing PL strain' (T3wt) is being heavily evaluated as an oncolytic and immunotherapeutic treatment for cancers. Mutations that promote reovirus entry into tumor cells were previously reported to enhance oncolysis; herein we aimed to discover mutations that enhance the post-entry steps of reovirus infection in tumor cells. Using directed evolution, we identified that reovirus variant T3v10M1 exhibited enhanced replication relative to T3wt on a panel of cancer cells. T3v10M1 contains an alanine-to-valine substitution (A612V) in the core-associated μ2, which was previously found to have NTPase activities in virions and to facilitate virus factory formation by association with μNS. Paradoxically, the A612V mutation in μ2 from T3v10M1 was discovered to impair NT

SUBMITTER: Yip WKW 

PROVIDER: S-EPMC8139653 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature