Infectious Bronchitis Virus Regulates Cellular Stress Granule Signaling

Abstract

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.

Inhibition of anti-viral stress granule formation by coronavirus endoribonuclease nsp15 ensures efficient virus replication

“…consistent with previous reports [43], also in our study we found that IBV inhibits both eIF2αdependent (heat shock, sodium arsenite) and -independent (NaCl) SGs formation. We also assessed SGs formation by PEDV infection, only 10%-20% of PEDV-infected Vero cells were SGs positive (S6 Fig).…”

“…During the course of our study, it was reported that IBV inhibits eIF2α-dependent and -independent SGs induction in Vero cells [ 43 ]. Here, we used H1299 and DF-1 cells to further investigate the inhibition of SGs by IBV.…”

“…During the course of our study, it was reported that IBV inhibits eIF2α-dependent and -independent SGs induction in Vero cells [43]. Here, we used H1299 and DF-1 cells to further Mock infection was included as negative control, poly I:C transfection for 6 h or 1 mM sodium arsenite for 30 min were included as positive control.…”

“…Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), SARS-CoV-2 and IBV N proteins have been found to interact with the key SG component G3BP1 [ 41 , 42 ]. A recent report shows that infectious bronchitis virus (IBV) infection results in the formation of SGs in approximately 20% of infected cells and inhibits eIF2α-dependent and -independent SG formation by unknown mechanisms [ 43 ].…”

Dance with the Devil: Stress Granules and Signaling in Antiviral Responses

“…While sequestration of viral RNAs in SGs is generally thought to represent an antiviral strategy, it is also possible that in some cases, viral replication might benefit from the concentration of viral RNAs in SGs. Given that many viruses including poliovirus, infectious bronchitis virus, mengovirus, and TMEV efficiently prevent the recruitment of viral RNAs into SGs [280,[374][375][376], it is reasonable to postulate that SGs primarily serve an antiviral function.…”