Transmembrane Protein 39A Promotes the Replication of Encephalomyocarditis Virus via Autophagy Pathway.

Xiangrong Li,Qian Li,Jingying Xie,Ruofei Feng,Shengjun Li,Jialin Bai,Ruixian Ma,Haixia Zhang,Adi Idris

doi:10.3389/fmicb.2019.02680

Abstract

Encephalomyocarditis virus (EMCV) causes encephalitis, myocarditis, neuropathy, reproductive disorders, and diabetes in animals. EMCV is known to induce cell autophagy; however, the molecular mechanisms underlying this remain unclear. Here, we show that the type III-transmembrane protein, transmembrane protein 39A (TMEM39A), plays a critical role in EMCV replication. We showed that EMCV GS01 strain infection upregulated TMEM39A expression. Importantly, EMCV induced autophagy in a range of host cells. The autophagy chemical inhibitor, 3-MA, inhibited EMCV replication and reduced TMEM39A expression. This is the first study demonstrating TMEM39A promoting the replication of EMCV via autophagy. Overall, we show that TMEM39A plays a positive regulatory role in EMCV proliferation and that TMEM39A expression is dependent on the autophagy pathway.

Highlights

Encephalomyocarditis virus (EMCV) is a positive sense single-stranded RNA virus belonging to the Picornaviridae family (Koenen, 2006)
We recently found that transmembrane protein 39A (TMEM39A) interacted with the EMCV capsid proteins, VP1 (BHK-21 cell cDNA library) and VP2 (HUVEC cell cDNA library) via the yeast two-hybrid assay
TMEMs can regulate cancer processes in a myriad of ways (Guo et al, 2015; Wrzesiński et al, 2015) and the TMEM39A family member has been a recent attention in cancer research (Tran et al, 2017)

Summary

Introduction

Encephalomyocarditis virus (EMCV) is a positive sense single-stranded RNA virus belonging to the Picornaviridae family (Koenen, 2006). EMCV is commonly used to study innate immune responses toward double-stranded RNA (dsRNA) (Carocci and Bakkali, 2012). EMCV infection is common in large-scale pig farms in China (Zhang et al, 2017). EMCV life cycle and molecular epidemiology are well studied (Bai et al, 2014; Feng et al, 2015, 2015; Liu et al, 2016; Luo et al, 2017; Zhang et al, 2017). Little is known about the factors that influence EMCV replication.

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Conclusion