Elucidating the Host Interactome of EV-A71 2C Reveals Viral Dependency Factors.

Ye Li,Leiliang Zhang,Guofeng Zhu,Xia Jian,Peiqi Yin

doi:10.3389/fmicb.2019.00636

Abstract

Viral protein 2C plays a critical role in EV-A71 replication. The discovery of 2C binding proteins will likely provide potential targets to treat EV-A71 infection. Here, we provide a global proteomic analysis of the human proteins that interact with the EV-A71 2C protein. TRIM4, exportin2, and ARFGAP1 were validated as 2C binding partners. Further functional studies revealed that TRIM4, exportin2, and ARFGAP1 were novel host dependency factors for EV-A71. Moreover, enteroviruses’ 2C family proteins interacted with exportin2 and ARFGAP1. In conclusion, our study provides a cellular interactome of the EV-A71 2C and identifies the proviral roles of TRIM4, exportin2, and ARFGAP1 in EV-A71 infection.

Highlights

Enterovirus A71 (EV-A71) is one of the major pathogens that leads to hand, foot and mouth disease (HFMD) in young children and infants, and has become a serious threat to global public health (Baggen et al, 2018)
Key components of COPI including coatomer and ADP Ribosylation Factor 1 (ARF1) have been identified as host factors for EV-A71 (Wang et al, 2014), we chose another COPI component ADP Ribosylation Factor GTPase Activating Protein 1 (ARFGAP1), from the hit for GFP-2C, for further study
We demonstrated that the EV-A71 2C protein interacted with Tripartite Motif Protein 4 (TRIM4), exportin2, and ARFGAP1

Summary

Introduction

Enterovirus A71 (EV-A71) is one of the major pathogens that leads to hand, foot and mouth disease (HFMD) in young children and infants, and has become a serious threat to global public health (Baggen et al, 2018). Development of effective anti-EV-A71 drugs have been hampered by the lack of a detailed understanding of the virus-host interactions that could represent amenable targets for antiviral therapy. Enterovirus A71 with a positive-stranded RNA genome belongs to the human enterovirus species A of the genus enterovirus within the family Picornaviridae (Baggen et al, 2018). The viral genome encodes a single polyprotein precursor which could be proteolytically cleaved to four structural and seven non-structural proteins. The non-structural protein 2C of EV-A71 with 329 amino acids directs replication complexes to cell membranes and contains NTPase and helicase activities (Yuan et al, 2018). EV-A71 2C recruited reticulon to the viral replication complex (Tang et al, 2007). Coatomer is required for EV-A71 replication and associates with 2C (Wang et al, 2012). By interacting with RelA, 2C inhibited the NF-kB pathway (Du et al, 2015)

Methods

Results

Conclusion