African swine fever virus pS273R antagonizes stress granule formation by cleaving the nucleating protein G3BP1 to facilitate viral replication

by Selleckchem | Sep 30 2023

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs are regulated by different stimulators including viral infection, which is involved in the antiviral activity of host cells to limit viral propagation. To survive, several viruses have been reported to execute various strategies, such as modulating SGs formation, to create optimal surroundings for viral replication. African swine fever virus (ASFV) is one of the most notorious pathogens in the global pig industry. However, the interplay between ASFV infection and SGs formation remains largely unknown. In this study, we found that ASFV infection inhibited SGs formation. Through SGs inhibitory screening, we found that several ASFV-encoded proteins are involved in inhibition of SGs formation. Among them, an ASFV S273R protein (pS273R), the only cysteine protease encoded by the ASFV genome significantly affected SGs formation. ASFV pS273R interacted with G3BP1, a vital nucleating protein of SGs formation. Furthermore, we found that ASFV pS273R cleaved G3BP1 at the G140-F141 to produce two fragments (G3BP1-N1-140 and G3BP1-C141-456). Interestingly, both of the pS273R-cleaved fragments of G3BP1 lost the ability to induce SGs formation and antiviral activity. Taken together, our finding reveals that the proteolytic cleavage of G3BP1 by ASFV pS273R is a novel mechanism by which ASFV counteracts host stress and innate antiviral responses.

Comments:

The study you described investigates the interplay between African swine fever virus (ASFV) infection and the formation of cytoplasmic stress granules (SGs), which are structures involved in storing mRNAs during stress-induced translation arrest. The researchers found that ASFV infection inhibits SGs formation. They conducted a screening to identify ASFV-encoded proteins responsible for this inhibition and discovered that ASFV S273R protein (pS273R), the only cysteine protease encoded by the ASFV genome, significantly affects SGs formation.

The researchers observed that ASFV pS273R interacts with G3BP1, an essential protein involved in nucleating SGs formation. They further found that ASFV pS273R cleaves G3BP1 at a specific site (G140-F141), resulting in the production of two fragments: G3BP1-N1-140 and G3BP1-C141-456. Intriguingly, both of these pS273R-cleaved fragments of G3BP1 lose the ability to induce SGs formation and exhibit reduced antiviral activity.

Based on their findings, the researchers propose that the proteolytic cleavage of G3BP1 by ASFV pS273R represents a novel mechanism through which ASFV counteracts host stress and innate antiviral responses. By inhibiting SGs formation, ASFV creates an optimal environment for its own replication and evades the antiviral defenses of the host cells.

This study provides new insights into the interaction between ASFV and the host cellular response, shedding light on the strategies employed by the virus to promote its survival and propagation.