Heat Shock Protein A6 Is Especially Involved in Enterovirus 71 Infection.

Jiaoyan Jia,Ran Yan,Qinchang Zhu,Zhendan He,Xun Song,Ge Liu,Jianfeng Zhong,Kai Zheng,Zhe Ren

doi:10.3389/fmicb.2022.865644

Abstract

Hand foot and mouth disease (HFMD) caused by Enterovirus 71 (EV71) infection is still a major infectious disease threatening children’s life and health in the absence of effective antiviral drugs due to its high prevalence and neurovirulence. A study of EV71-specific host response might shed some light on the reason behind its unique epidemiologic features and help to find means to conquer EV71 infection. We reported that host heat shock protein A6 (HSPA6) was induced by EV71 infection and involved infection in both Rhabdomyosarcoma (RD) cells and neurogliocytes. Most importantly, we found that EV71 did not induce the expression of other heat shock proteins HSPA1, HSPA8, and HSPB1 under the same conditions, and other HFMD-associated viruses including CVA16, CVA6, CVA10, and CVB1-3 did not induce the upregulation of HSPA6. In addition, EV71 infection enhanced the cytoplasmic aggregation of HSPA6 and its colocalization with viral capsid protein VP1. These findings suggest that HSPA6 is a potential EV71-specific host factor worthy of further study.

Highlights

Enterovirus 71 (EV71) from the Picornaviridae family is one of the common causative pathogens for hand foot and mouth disease (HFMD), which is usually a self-limiting, mild childhood disease with typical clinical manifestations of fever, mouth sores, skin rash on hands, mouth, and/or feet (Wong et al, 2010)
We show that EV71 did not induce the expression of HSPA1, HSPA8, and HSPB1 under the same conditions, and several other common Hand foot and mouth disease (HFMD)-associated viruses did not induce the upregulation of heat shock protein A6 (HSPA6)
Comparative transcriptome analysis was firstly performed and found that the expression of HSPA6 mRNA was upregulated in EV71 infected RD cells (Figure 1A), which could be inhibited by the treatment of penduletin (PDL), an active compound against EV71 we previously reported

Summary

Introduction

Enterovirus 71 (EV71) from the Picornaviridae family is one of the common causative pathogens for hand foot and mouth disease (HFMD), which is usually a self-limiting, mild childhood disease with typical clinical manifestations of fever, mouth sores, skin rash on hands, mouth, and/or feet (Wong et al, 2010). It can cause neurological complications such as myocarditis, aseptic meningitis, encephalitis, neurogenic pulmonary edema, and even death in severe cases.

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