The Kinase STK3 Interacts with the Viral Structural Protein VP1 and Inhibits Foot-and-Mouth Disease Virus Replication.

Huisheng Liu,Haixue Zheng,Qiaoying Zeng,Qiao Xue,Zixiang Zhu

doi:10.1155/2017/2481348

Abstract

Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180–214) of VP1 was essential for its interaction with STK3. The effects of overexpression and underexpressing of STK3 in PK-15 cells were assessed, and the results indicated that STK3 significantly inhibited FMDV replication. Our data expand the role of STK3 during viral infection, provide new information regarding the host cell kinases that are involved in viral replication, and identify potential targets for future antiviral strategies.

Highlights

Foot-and-mouth disease virus (FMDV), a positive-sense, single-stranded RNA virus, is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals, including cattle, pigs, sheep, goats, camelids, and deer [1, 2]
To identify the host cellular proteins interacting with VP1 of FMDV, the FMDV VP1 was expressed as an amino-terminal fusion to the GAL4-DNA-binding domain
The potential mechanisms by which FMDV proteins interact with host cell proteins are not fully understood

Summary

Introduction

Foot-and-mouth disease virus (FMDV), a positive-sense, single-stranded RNA virus, is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals, including cattle, pigs, sheep, goats, camelids, and deer [1, 2]. Seven serotypes (A, O, C, Asia, SAT1, SAT2, and SAT3) and numerous subtypes of FMDV have been identified, and no cross-protection has been reported among the different serotypes [3, 4]. The FMDV genome is approximately 8.5 kb in length, and it encodes a single polyprotein that is posttranslationally processed into four structural proteins (VP1, VP2, VP3, and VP4) and eight nonstructural proteins (Lpro, 2A, 2B, 2C, 3A, 3B, 3Cpro, and 3D) [5]. The proteins VP0, VP1, VP3, Lpro, 2B, 3A, and 3Cpro have been reported to play roles in inhibiting or evading the host innate immune system [5,6,7,8,9,10,11,12,13]. VP1, an important viral protein that plays an essential role in FMDV pathogenesis, carries the major neutralizing antigenic sites, and the VP1 gene has been used widely in epidemiological investigations of FMDV, vaccine development, and the establishment of diagnostic methods [17, 18]

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