The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A

Yan Xiao,Xia Xiao,Xiaobo Lei,Yijie Ma,Bin He,Chao Wu,Jianwei Wang,Zhuo Zhou,Jianli Qi,Zhenzhen Zhang

doi:10.1038/srep44592

Abstract

Enterovirus 71 (EV71) is a human pathogen that causes hand, foot, mouth disease and neurological complications. Although EV71, as well as other enteroviruses, initiates a remodeling of intracellular membrane for genomic replication, the regulatory mechanism remains elusive. By screening human cDNA library, we uncover that the Golgi resident protein acyl-coenzyme A binding domain-containing 3 (ACBD3) serves as a target of the 3A protein of EV71. This interaction occurs in cells expressing 3A or infected with EV71. Genetic inhibition or deletion of ACBD3 drastically impairs viral RNA replication and plaque formation. Such defects are corrected upon restoration of ACBD3. In infected cells, EV71 3A redirects ACBD3, to the replication sites. I44A or H54Y substitution in 3A interrupts the binding to ACBD3. As such, viral replication is impeded. These results reveal a mechanism of EV71 replication that involves host ACBD3 for viral replication.

Highlights

Enterovirus 71 (EV71) is a single-stranded, positive-sense RNA virus
Our results demonstrate that EV71 3A selectively utilizes ACBD3 to facilitate viral replication
ACBD3 is a cellular target of the 3A protein encoded by EV71

Summary

Introduction

EV71 is a single-stranded, positive-sense RNA virus. The viral genome is approximately 7,500 nucleotides in length, with a single open reading frame that encodes a large precursor protein. Further experiments reveal that GBF1 and ARF1 play a minor role on EV71 RNA replication and protein expression. EV71 3A interacts with endogenous ACBD3 in virus-infected cells. After 24 h, cell lysates were immunoprecipitated with antibody against ACBD3. In GFP-3A-expressing cells ACBD3 dispersed into the cytoplasm and co-localized with 3A (Fig. 2a, lower).

Results

Conclusion