Multiple regulatory effects of HSP27 on the proliferation of encephalomyocarditis virus in vitro

Abstract:

[Objective] We explored the regulatory effects of heat shock protein 27 (HSP27) on various signaling pathways during the proliferation of encephalomyocarditis virus (EMCV) in vitro, aiming to lay a foundation for deciphering the mechanism of other host factors in regulating EMCV proliferation in vitro and provide evidence for comprehensively revealing the pathogenic mechanism of EMCV. [Methods] Real-time quantitative PCR (RT-qPCR), Western blotting, indirect immunofluorescence, and nucleocytoplasmic separation were employed to evaluate the effects of the knockdown and overexpression of HSP27 on the EMCV infection-induced autophagy, eukaryotic translation initiation factor 2α subunit 1 (EIF2S1)-activating transcription factor 4 (ATF4) signaling pathway, and myeloid differentiation factor 88 (MyD88)/nuclear transcription factor kappa B (NF-κB) signaling pathway.[Results] Interfering with the expression of HSP27 in host cells promoted autophagy and activated EIF2S1-ATF4 signaling pathway, and inhibited EMCV-induced activation of MyD88/NF-κB signaling pathway. On the contrary, overexpression of HSP27 not only reduced EMCV-induced autophagy and inhibited EIF2S1-ATF4 signaling pathway, but also up-regulated the expression of the proteins in MyD88/NF-κB signaling pathway and promoted the nuclear translocation of p65 and the transcription of inflammation-related cytokines.[Conclusion] HSP27 can not only negatively regulate EMCV-induced autophagy by inhibiting the EIF2S1-ATF4 signaling pathway, but also positively regulate the EMCV-triggered MyD88/NF-κB signaling pathway, playing multiple regulatory roles in EMCV infection.