A poxvirus pseudokinase represses viral DNA replication via a pathway antagonized by its paralog kinase.

ABSTRACT: Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that mutations correlating with a loss of function of the vaccinia B12 pseudokinase provide a striking fitnes

SUBMITTER: Olson AT 

PROVIDER: S-EPMC6395007 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature