The Mechanism of Enterovirus 71 Induced Heat Shock Protein 27 Response to Promote Viral Infection.

摘要

The outbreaks of enterovirus 71 (EV71) infections have become a major public health issue worldwide, especially in the Asia-Pacific region. EV71 infection can be asymptomatic or cause diarrhea, rashes, and hand, foot, and mouth disease (HFMD). However, EV71 can also cause severe neurological disease even death. To date, little is known about the molecular mechanisms of the host response to EV71 infection. In this study, the expression patterns of host genes in EV71 infected human rhabdomyosarcoma cells were analyzed by using two-dimensional proteomics assays. In total, 42 protein spots were found to be differentially expressed (>2 fold changes, p<0.05) in three pairs of gels, of which 21 proteins were found to be down-regulated while 21 were up-regulated. Data analysis suggested that proteins associated with metabolic process, biological regulation, cellular component organization, cell communication and death were most modified. HSP27, one of the most altered proteins during EV71 infection, was selected to determine its fundamental roles upon EV71 infection. We show that HSP27 is rapidly upregulated both at the transcriptional and the translational levels at the early stage of EV71 infection. Depleting cellular HSP27 expression reduced EV71 replication, while overexpression of HSP27 greatly enhanced viral infection. By using the phosphorylated specific antibodies, serine residues 15, 78, but not the 82 were found to be phosphorylated during EV71 infection. The phosphorylation depended on the activation of the mitogen-activated protein kinase p38 signaling pathway. After treating with p38 kinase inhibitors, EV71 replication was coordinately decreased. Further analysis showed ii that HSP27 affected the protease 2A mediated eIF4G cleavage and assisted the IRES driven translation, thus facilitated the EV71 replication. The findings in this work not only provided a global view of the host responses to EV71 infection, but demonstrated HSP27 to be a valid target for anti-EV71 drug development.