Subjugating Translational Inhibition in Response to Ribosomal Protein Insufficiency by a Herpesvirus Ribosome-Associated Protein

Vink, E. I.; Andrews, J.; Duffy, C.; Mohr, I.

doi:10.1101/2020.10.11.334607

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bioRxiv · 10.1101/2020.10.11.334607

Subjugating Translational Inhibition in Response to Ribosomal Protein Insufficiency by a Herpesvirus Ribosome-Associated Protein

Vink, E. I.·Andrews, J.·Duffy, C.·Mohr, I.

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Abstract

In addition to being required for protein synthesis, ribosomes and ribosomal proteins (RPs) also regulate mRNA translation in uninfected and virus-infected cells. By individually depleting 85 RPs using RNAi, we found overall protein synthesis in uninfected primary fibroblasts was more sensitive to RP-depletion than those infected with herpes simplex virus-1 (HSV-1). Although representative RP-depletion (uL3, uS4, uL5) inhibited protein synthesis in cells infected with other DNA viruses, HSV-1-infected cell protein synthesis unexpectedly endured and required a single virus-encoded gene product, VP22. During individual RP-insufficiency, VP22-expressing HSV-1 replicated better than a VP22-deficient variant. Furthermore, VP22 cosedimented with ribosomes and polyribosomes in infected cells. This identifies VP22 as a virus-encoded, polyribosome-associated protein that compensates for RP-insufficiency to support viral protein synthesis and replication. Moreover, it reveals an unanticipated class of virus-encoded, ribosome-associated effectors that reduce the dependence of protein synthesis upon RPs and broadly support translation during physiological stress such as infection.

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Vink, E. I., Andrews, J., Duffy, C., Mohr, I.. 2020-10-11. Subjugating Translational Inhibition in Response to Ribosomal Protein Insufficiency by a Herpesvirus Ribosome-Associated Protein. https://doi.org/10.1101/2020.10.11.334607

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