A little less aggregation a little more replication: Viral manipulation of stress granules.

Recent exciting studies have uncovered how membrane-less organelles, also known as biocondensates, are providing cells with rapid response pathways, allowing them to re-organize their cellular contents and adapt to stressful conditions. Their assembly is driven by the phase separation of their RNAs and intrinsically disordered protein components into condensed foci. Among these, stress granules (SGs) are dynamic cytoplasmic biocondensates that form in response to many stresses, including activation of the integrated stress response or viral infections. SGs sit at the crossroads between antiviral signaling and translation because they concentrate signaling proteins and components of the innate immune response, in addition to translation machinery and stalled mRNAs. Consequently, they have been proposed to contribute to antiviral activities, and therefore are targeted by viral countermeasures. Equally, SGs components can be commandeered by viruses for their own efficient replication. Phase separation processes are an important component of the viral life cycle, for example, driving the assembly of replication factories or inclusion bodies. Therefore, in this review, we will outline the recent understanding of this complex interplay and tug of war between viruses, SGs, and their components. This article is categorized under: RNA in Disease and Development > RNA in Disease Translation > Regulation RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

Ribopuromycylation in Coronavirus-Infected Cells.

Ribopuromycylation enables the visualization and quantitation of translation on a cellular level by immunofluorescence or in total using standard western blotting. This technique uses ribosome catalyzed puromycylation of nascent chains followed by immobilization on the ribosome by antibiotic chain elongation inhibitor emetine. Detection of puromycylated ribosome-bound nascent chains can then be achieved using a puromycin-specific antibody.

Infectious Bronchitis Virus Regulates Cellular Stress Granule Signaling.

Viruses must hijack cellular translation machinery to express viral genes. In many cases, this is impeded by cellular stress responses. These stress responses result in the global inhibition of translation and the storage of stalled mRNAs, into RNA-protein aggregates called stress granules. This results in the translational silencing of the majority of mRNAs excluding those beneficial for the cell to resolve the specific stress. For example, the expression of antiviral factors is maintained during viral infection. Here we investigated stress granule regulation by Gammacoronavirus infectious bronchitis virus (IBV), which causes the economically important poultry disease, infectious bronchitis. Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways, whilst at the same time, IBV replication also results in the induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. These results provide novel insights into how IBV modulates cellular translation and antiviral stress signaling.