Multiple functions of stress granules in viral infection at a glance

Abstract

Stress granules (SGs) are distinct RNA granules induced by various stresses, which are evolutionarily conserved across species. In general, SGs act as a conservative and essential self-protection mechanism during stress responses. Viruses have a long evolutionary history and viral infections can trigger a series of cellular stress responses, which may interact with SG formation. Targeting SGs is believed as one of the critical and conservative measures for viruses to tackle the inhibition of host cells. In this systematic review, we have summarized the role of SGs in viral infection and categorized their relationships into three tables, with a particular focus on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Moreover, we have outlined several kinds of drugs targeting SGs according to different pathways, most of which are potentially effective against SARS-CoV-2. We believe this review would offer a new view for the researchers and clinicians to attempt to develop more efficacious treatments for virus infection, particularly for the treatment of SARS-CoV-2 infection.

TRIM25 predominately associates with anti-viral stress granules

“…In contrast, Chemotherapy drugs like selenite or UV exposure led to the formation of noncanonical SGs, which are less dynamic and pro-apoptotic to cells 15 , 16 . Although the concept of stress-specific SG subtypes is emerging 7 , 15 , 17 – 19 , their different protein and RNA compositions and functions are largely unexplored.…”

“…The formation of SGs is an integral part of the innate immune response to viral infection 7 . All viruses require the translation machinery of the host cell to synthesize viral proteins 5 , 20 .…”

“…SGs can serve as a platform for the assembly of antiviral signaling pathways, such as the interferon response. For instance, many viral sensors, such as melanoma differentiation-associated Protein 5 (MDA5), retinoic acid-inducible gene I (RIG-I), and the double-stranded RNA-dependent protein kinase (PKR), are recruited to SGs to initiate antiviral responses 7 . The central proteins in SGs, G3BP1/2, promote both inflammatory and type I interferon (IFN) responses 21 – 23 .…”

The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions

“…Furthermore, viruses dampen innate immune signaling by interfering with distinct steps in the cellular signaling cascades. A common target of viruses is to disrupt the formation of stress granules which have been implicated as signaling hubs for antiviral signaling (Guan et al, 2023 ; Lloyd, 2013 ; McCormick and Khaperskyy, 2017 ; Miller, 2011 ). Stress granules, large membrane-less protein-RNA assemblies, form in the cytoplasm in response to various stress signals, including viral infections (Protter and Parker, 2016 ).…”

Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease

“…Interestingly, previous studies have demonstrated that EV71-2A pro is capable of manipulating host cell gene expression through the cleavage of various proteins, such as eIF4GI, eIF4GII, PABP, and P-body ( 6 , 21 , 22 ). In response to antiviral cellular immune defense, host cells accumulate a significant number of proteins and RNAs in the cytoplasm, resulting in the formation of envelope-free emergency granules known as stress granules (SGs) ( 23 ). The interaction between eIF4GI-RasGAP SH3 domain binding protein plays a crucial role in the conversion of typical stress granules (tSGs) into atypical stress granules (aSGs), thereby facilitating the infection caused by EV71 ( 21 , 24 ).…”