Alphavirus nsP3 ADP-ribosylhydrolase Activity Disrupts Stress Granule Formation

Aravinth Kumar Jayabalan; Diane E. Griffin; Anthony K. L. Leung

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. [25, 26, 29] . It would be of interest to explore whether PAR plays a role in re-assortment of proteins in non-membranous structures in general. Our analyses further revealed that the essential SG component G3BP1 is one of the nsP3 ADP-ribosylhydrolase targets. However, it is unclear whether the observed re-assortment of SG composition is mediated by ADP-ribosylation of G3BP1 and/or other targets within SGs, which warrants further investigation. The observed pattern of specific protein retainment suggests that some protein-protein interaction networks within SGs are mediated by PAR, with the possibility that the ADP-ribosylhydrolase activity of nsP3 actively promotes the release from SGs of translation factors needed for viral protein translation (Fig. 4d) . Such a possibility is consistent with recent data showing that nsP3 ADP-ribosylhydrolase activity is critical for switching from host translation to translation of the viral structural proteins during the later stages of viral replication [68, 69] . All rights reserved. No reuse allowed without permission.