Rabbit Anti-Human G3BP1 Polyclonal antibody

In response to stress, cells induce ribonucleoprotein aggregates, termed stress granules (SGs). SGs are transient loci containing translation-stalled mRNA, which is eventually degraded or recycled for translation. Infection of some viruses, including influenza A virus with a deletion of nonstructural protein 1 (IAV Delta NS1), induces SG-like protein aggregates. Previously, we showed that IAV Delta NS1-induced SGs are required for efficient induction of type I interferon (IFN). Here, we investigated SG formation by different viruses using green fluorescent protein (GFP)-tagged Ras-Gap SH3 domain binding protein 1 (GFP-G3BP1) as an SG probe. HeLa cells stably expressing GFP-G3BP1 were infected with different viruses, and GFP fluorescence was monitored live with time-lapse microscopy. SG formations by different viruses was classified into 4 different patterns: no SG formation, stable SG formation, transient SG formation, and alternate SG formation. We focused on encephalomyocarditis virus (EMCV) infection, which exhibited transient SG formation. We found that EMCV disrupts SGs by cleavage of G3BP1 at late stages of infection (>8 h) through a mechanism similar to that used by poliovirus. Expression of a G3BP1 mutant that is resistant to the cleavage conferred persistent formation of SGs as well as an enhanced induction of IFN and other cytokines at late stages of infection. Additionally, knockdown of endogenous G3BP1 blocked SG formation with an attenuated induction of IFN and potentiated viral replication. Taken together, our findings suggest a critical role of SGs as an antiviral platform and shed light on one of the mechanisms by which a virus interferes with host stress and subsequent antiviral responses.

Stress granules are evolutionally conserved ribonucleoprotein structures that are formed in response to various stress stimuli. Recent studies have demonstrated that proteins with low complexity (LC) regions play a critical role for the formation of stress granules. In this study, we report that FAM98A, whose biological functions are unknown, is a novel component of stress granules. FAM98A is localized to stress granules, but not to P-bodies, after various stress stimuli. Analysis with deletion mutants revealed that C-terminal region that contains LC region was essential for FAM98A accumulation to stress granules. Depletion of FAM98A using two different siRNAs decreased the number of stress granules formed per cell. Finally, we show that FAM98A associates with stress granule-localized proteins, such as DDX1, ATXN2, ATXN2L, and NUFIP2. Our results show a partial role of FAM98A for the organization of stress granules.