Proteomic analysis of polysomes isolated from human cells infected with polio, zika or dengue viruses

ABSTRACT: Viral pathogens are an ongoing threat to public health worldwide. Dissecting their dependence on host biosynthetic pathways could lead to effective antiviral therapies. To define how entero- and flaviviruses redirect host ribosomes to synthesize viral proteins and disable host protein production, we performed proteomic analysis of lysates and isolated polysomes from human Huh7 cells infected with either polio, zika or dengue viruses. We find that infection remodels polysome composition along similar principles, without major changes to core ribosome stoichiometry. These viruses use different strategies to evictfrom polysomes a common set of translation initiation and RNA surveillance factors while recruiting host machineries specifically required for viral biogenesis. We also find that both zika and dengue utilize the collagen prolyl-hydroxylation machinery to mediate co-translational modification of conserved prolines in the viral polyprotein. Our findings show how RNA viruses co-opt polysome modularity and establish a powerful strategy to identify targets for selective antiviral interventions.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Cell Culture

SUBMITTER: Ranen Aviner  

LAB HEAD: Raul Andino

PROVIDER: PXD024546 | Pride | 2021-08-17

REPOSITORIES: Pride