Stress granules formed during infections with RNA viruses have significant virus-specific differences in generation and composition.

Authors

Reto M Lang, Silvio Steiner, Jenna Kelly, Anne-Christine Uldry, Pratik Dave, Sophie Braga-Lagache, Jeffrey Chao, Manfred Heller, G Tuba Barut, Volker Thiel

Published in

PLoS biology. Volume 24. Issue 8. Pages e3003363. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

Eukaryotic cells evolved a cellular stress response to cope with extrinsic and intrinsic stress stimuli including virus infections. The major result of this response is the shutdown of bulk translation to prevent damage and allow the reprogramming of translation towards stress-resolving pathways. The resulting translationally stalled mRNA and associated proteins are accumulated in membrane-less cytosolic condensates called stress granules (SG). While the inhibitory effect of translation arrest on virus growth is well established, the role of SGs in the cellular defense against viruses is still unclear. The observation of specific interference with SG formation during various virus infections led to the hypothesis that SGs could serve as antiviral signaling platforms. In this study, we used mouse hepatitis virus (MHV) to characterize SGs formed during coronavirus infection. By applying APEX2-mediated proximity labeling in combination with quantitative proteomics, we dissected the proteome of MHV-induced granules and compared it to canonical SGs formed during oxidative stress. Our data revealed substantial differences in protein abundance and composition, indicating stressor-specific SG characteristics. To assess if the observed differences are a general feature of virus-induced SGs or rather virus-specific, we extended our investigations to the Semliki Forest virus (SFV), a member of the alphavirus family known to induce SGs. An initial comparison of SG formation kinetics by live-cell imaging showed distinct time points of SG induction between both viruses. A comprehensive comparison of the SG protein compositions revealed profound differences in the SG proteome between SFV and MHV. A further subcellular localization of SG components by microscopy not only confirmed a reduced abundance of several translation initiation factors in MHV-induced granules, but surprisingly, revealed the presence of SFV RNA and the absence of MHV RNA in virus-induced SGs. The reduced connection to canonical SG themes observed for MHV-induced granules compared to SFV- and oxidative stress-induced ones indicates a different impact of these condensates on MHV replication and further raises the question whether they should be considered SGs. The surprising plasticity of SGs concerning induction kinetics, protein composition and abundance, and inclusion or exclusion of viral RNA provide a base for future investigations of the role(s) of SGs in the context of viral infection and how they may impact virus replication.

PMID:
42600036
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.