| Enterovirus 71 (EV71) is the major causative pathogen of hand, foot, and mouth disease (HFMD). Acute EV71 infection can lead to severe neurological manifestations and occasionally cause permanent paralysis or death. In recent years, the morbidity and mortality of hand, foot, and mouth disease caused by EV71 showed a substantial rise in China and the infection of EV71 has become a serious public health problem. Currently, the underlying pathogenic mechanisms induced by EV71 are still unclear, andthere are no effective and specific anti-viral. Therefore, further research is still needed to elucidate EV71 pathogenesis.Stress granule (SG) is the important constituent of host defense system, it plays an important role in antiviral infection. Many studies have suggested that different viruses can modulate SG formation with different effects, and the virus-SG relationship may correlate to viral pathogenicity. However, the exact mechanism of EV71 infection induced SGs and how SGs regulate the virus replication are still uncertain.Therefore, this study aimed to conduct in-depth research on the mutual regulative relationship between EV71 and SGs. Through detecting the localization of typical components of SG in EV71 infected cells, we found that EV71 inhibits canonical SGs formation in infected cells and induces the formation of novel RNA granules that were distinguished from canonical SGs in composition and morphology, which we termed’SG like structures’. Further study showed that EV71 triggered formation of SG-like structures is dependent on PKR and eIF2a phosphorylation and requires ongoing cellular mRNA synthesis. By inhibiting the formation of SG-like, we found that SG-like structures are antiviral RNA granules that promote cellular apoptosis and suppress EV71 propagation. Taken together, our findings further illuninate the formation mechanism of SG-like structures induced by EV71 and shed light on virus-host interaction and molecular mechanism underlying EV71 pathogenesis. |
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