Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects.

Jing Jin,Wenbiao Wang,Sha Ai,Kailang Wu,Weiyong Liu,Qi Zhang,Yu Song,Yingle Liu,Jianguo Wu,Zhen Luo

doi:10.3390/v12010022

Abstract

Enterovirus 71 (EV71) infection causes hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby presenting a serious risk to public health. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially show that the interleukin enhancer-binding factor 2 (ILF2) reduces EV71 50% tissue culture infective dose (TCID50) and attenuates EV71 plaque-formation unit (PFU), thereby repressing EV71 infection. Microarray data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) -differentiated macrophages and human rhabdomyosarcoma (RD) cells. In addition, EV71 nonstructural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm, and it colocalizes with 2B in the cytoplasm. Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein.

Highlights

Enterovirus 71 (EV71), a positive-stranded RNA virus, is a member of the Enterovirus genus within the family Picornaviridae [1,2]
We demonstrated that EV71 nonstructural protein 3D binds to the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3, the sensor component of NLRP3 inflammasome) to enhance inflammasome activation [34], and that Interleukin enhancer-binding factor 2 (ILF2) interacts with NLRP3 to inhibit inflammasome activation [35]
Upon EV71 infection, EV71 3C was attenuated in ILF2-lentivirus cells as compared with CT-lentivirus cells (Figure 1B), demonstrating that ILF2 represses EV71 replication

Summary

Introduction

Enterovirus 71 (EV71), a positive-stranded RNA virus, is a member of the Enterovirus genus within the family Picornaviridae [1,2]. EV71 infection may cause hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and fatal encephalitis in children [3,4]. EV71 has a signal-stranded, positive-sense RNA genome with one open reading frame that encodes a polyprotein of approximately. Upon EV71 infection, the protein precursor is cleaved into four structural proteins (VP1, VP2, VP3, and VP4) and seven nonstructural proteins (2A, 2B, 2C, 3A, 3B, 3C, and 3D) [6]. Interleukin enhancer-binding factor 2 (ILF2) is a transcriptional activator which regulates interleukin 2 (IL-2) expression [11].

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Results

Conclusion