Hiding in Plain Sight: Formation and Function of Stress Granules During Microbial Infection of Mammalian Cells

Alistair Tweedie; Tracy Nissan

doi:10.3389/fmolb.2021.647884

Hiding in Plain Sight: Formation and Function of Stress Granules During Microbial Infection of Mammalian Cells

Front Mol Biosci. 2021 Apr 29:8:647884. doi: 10.3389/fmolb.2021.647884. eCollection 2021.

Authors

Alistair Tweedie¹, Tracy Nissan^{1

2}

Affiliations

¹ Department of Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Brighton, United Kingdom.
² Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

Abstract

Stress granule (SG) formation is a host cell response to stress-induced translational repression. SGs assemble with RNA-binding proteins and translationally silent mRNA. SGs have been demonstrated to be both inhibitory to viruses, as well as being subverted for viral roles. In contrast, the function of SGs during non-viral microbial infections remains largely unexplored. A handful of microbial infections have been shown to result in host SG assembly. Nevertheless, a large body of evidence suggests SG formation in hosts is a widespread response to microbial infection. Diverse stresses caused by microbes and their products can activate the integrated stress response in order to inhibit translation initiation through phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). This translational response in other contexts results in SG assembly, suggesting that SG assembly can be a general phenomenon during microbial infection. This review explores evidence for host SG formation in response to bacterial, fungal, and protozoan infection and potential functions of SGs in the host and for adaptations of the pathogen.

Keywords: GCN2; HRI; PERK; PKR; eIF2 alpha; integrated stress response (ISR); stress granules (SG); unfolded protein response (UPR).

Publication types

Review