Format

Send to

Choose Destination
Antiviral Res. 2018 Feb;150:39-46. doi: 10.1016/j.antiviral.2017.11.020. Epub 2017 Nov 24.

Hsc70 regulates the IRES activity and serves as an antiviral target of enterovirus A71 infection.

Author information

1
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
2
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; Jockey Club of School of Public Health, Chinese University of Hong Kong, Hong Kong, China.
3
Departments of Surgery, Faculty of Medicine, Chinese University of Hong Kong, China.
4
Jockey Club of School of Public Health, Chinese University of Hong Kong, Hong Kong, China.
5
Jockey Club of School of Public Health, Chinese University of Hong Kong, Hong Kong, China. Electronic address: maggiew@cuhk.edu.hk.
6
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; Biotechnology and Health Center, CityU Shenzhen Research Institute, Shenzhen, China. Electronic address: mlhe7788@gmail.com.

Abstract

Enterovirus A71 (EV-A71) is a small positive-stranded RNA virus that causes human hand, foot and mouth disease (HFMD) and fatal neurological disorders in some cases without effective treatment. Here we show that heat shock cognate protein 70 (Hsc70), a molecular chaperone, displays pivotal role in viral infections. Knockdown of Hsc70 significantly suppresses viral replication evidenced by reducing not only the level of both viral replication intermediates (negative stranded RNA) and viral genomic RNA (positive stranded RNA), but also the level of viral protein expression; whereas ectopic expression of Hsc70 markedly promotes viral replication. Interestingly, depletion of Hsc70 decreases the IRES activity of EV-A71, and the ectopic expression of Hsc70 enhances the IRES activity accordingly. Further study shows that Hsc70 binds viral genomic RNA but does not directly interact with IRES. Moreover, we reveal that Hsc70 interacts with 2A protease and promotes eIF4G cleavage. More importantly, Hsc70 inhibitor Ver-155008 significantly protects cytopathic effects from EV-A71 infection and inhibits both IRES activity and viral reproduction in a dose-dependent manner. The cell viability assay shows that the IC50 and CC50 are 2.01 μM and 47.67 μM, respectively. These results demonstrate not only an important mechanism of Hsc70 in facilitating EV-A71 replication, but also a target for antiviral drug development.

PMID:
29180285
DOI:
10.1016/j.antiviral.2017.11.020
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center