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Open Access Highly Accessed Research

Nonstructural proteins 2C and 3D are involved in autophagy as induced by the encephalomyocarditis virus

Lei Hou, Xinna Ge, Lingxiang Xin, Lei Zhou, Xin Guo* and Hanchun Yang*

Author Affiliations

Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People’s Republic of China

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Virology Journal 2014, 11:156  doi:10.1186/1743-422X-11-156

Published: 1 September 2014

Abstract

Background

Encephalomyocarditis virus (EMCV) can infect a variety of animal species and humans. Although the EMCV infection is known to induce autophagy to promote its replication in host cells, the viral proteins that are responsible for inducing autophagy are unknown.

Methods

The recombinant plasmids that were expressing the EMCV proteins were constructed to analyze the role of each protein in the induction of autophagy. Autophagy inductions by the EMCV proteins in BHK-21 cells were investigated by confocal microscopy, Western blotting and transmission electron microscopy. ER stress in BHK-21 cells was examined by detecting the marker molecules using western blotting and luciferase assays.

Results

This study presents the first demonstration that the nonstructural proteins 2C or 3D of EMCV were involved in inducing autophagy in BHK-21 cells that were expressing 2C or 3D, and we found that inhibiting Beclin1 expression influenced this autophagy induction process. Next, 2C and 3D were shown to be involved in inducing autophagy by activating the ER stress pathway. Finally, EMCV 2C or 3D were demonstrated to regulate the proteins associated with PERK and ATF6alpha pathway.

Conclusions

Our findings indicate that 2C and 3D are involved in EMCV-induced autophagy by activating ER stress molecules and regulating the proteins expression associated with UPR pathway, helping to better understand the EMCV-induced autophagy process.

Keywords:
Encephalomyocarditis virus (EMCV); Nonstructural protein; 2C; 3D; Autophagy; Endoplasmic reticulum (ER) stress; Unfolded protein response (UPR)