Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication.

Qi Xiang,Siyu Huang,Kailang Wu,Mengying Qin,Pin Wan,Jianguo Wu,Zhen Luo,Ge Yang,Hua Yang

doi:10.3390/v12070756

Abstract

Enterovirus 71 (EV71) is the main pathogen causing hand-foot-mouth disease (HFMD) in infants and children, which can also lead to severe neurological diseases and even death. Therefore, understanding the replication mechanism of EV71 is of great significance for the prevention and control of EV71-induced diseases. Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) is an important core protein for the initiation and the normal process of autophagy in cells. In addition to its involvement in autophagy, Beclin1 has also been reported to play an important role in cancer and innate immune signaling pathways. However, the role of Beclin1 in EV71 replication remains elusive. Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. Further studies discovered that Beclin1 could interacts with EV71 non-structural protein 3D mainly through its evolutionary conserved domain (ECD) and coiled-coiled domain (CCD), thus promoting the replication of EV71 in human rhabdomyosarcoma (RD) cells and human astroglioma (U251) cells. Collectively, we reveal a novel regulatory mechanism associated with Beclin1 to promote EV71 replication, thus providing a potential therapeutic target for the prevention and control of EV71-associated diseases.

Highlights

Enterovirus 71 (EV71) is a single-stranded positive RNA virus of the Picornaviridae family with a genome of approximately 7.5 kb
We firstly revealed that autophagy was induced, but Beclin1 was not significantly affected at either mRNA level or protein level in rhabdomyosarcoma (RD) cells infected with EV71
When studying Beclin1 as a core protein for the initiation and normal process of autophagy in cells, we firstly verified whether autophagy was induced during EV71 infection

Summary

Introduction

Enterovirus 71 (EV71) is a single-stranded positive RNA virus of the Picornaviridae family with a genome of approximately 7.5 kb. The P2 and P3 genomic regions encode the nonstructural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D [1]. EV71 causes hand, foot and mouth disease (HFMD) and can even cause fatal central nervous system (CNS) infections in young children, including encephalitis, aseptic meningitis and acute flaccid paralysis [2]. Since it was first identified from a child with neurologic symptoms in California in 1969 [3], epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported worldwide especially in the Asia-Pacific region [4,5,6,7,8,9]

Methods

Results

Conclusion