High-Order Epistasis and Functional Coupling of Infection Steps Drive Virus Evolution toward Independence from a Host Pathway.

ABSTRACT: The phosphatidylinositol-4 kinase IIIβ (PI4KB)/oxysterol-binding protein (OSBP) family I pathway serves as an essential host pathway for the formation of viral replication complex for viral plus-strand RNA synthesis; however, poliovirus (PV) could evolve toward substantial independence from this host pathway with four mutations. Recessive epistasis of the two mutations (3A-R54W and 2B-F17L) is essential for viral RNA replication. Quantitative analysis of effects of the other two mutations (2B-Q20H and 2C-M187V) on each step of infection reveals functional couplings between viral replication, growth, and spread conferred by the 2B-Q20H mutation, while no enhancing effect was conferred by the 2C-M187V mutation. The effects of the 2B-Q20H mutation occur only via another recessive epistasis be

SUBMITTER: Arita M 

PROVIDER: S-EPMC8557862 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature