Inhibition of aldolase A blocks biogenesis of ATP and attenuates Japanese encephalitis virus production

Chih-Feng Tien; Shih-Ching Cheng; Yen-Peng Ho; Yi-Shiuan Chen; Jung-Hsin Hsu; Ruey-Yi Chang

doi:10.1016/j.bbrc.2013.11.128

Inhibition of aldolase A blocks biogenesis of ATP and attenuates Japanese encephalitis virus production

Biochem Biophys Res Commun. 2014 Jan 10;443(2):464-9. doi: 10.1016/j.bbrc.2013.11.128. Epub 2013 Dec 7.

Authors

Chih-Feng Tien¹, Shih-Ching Cheng¹, Yen-Peng Ho², Yi-Shiuan Chen¹, Jung-Hsin Hsu¹, Ruey-Yi Chang³

Affiliations

¹ Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
² Department of Chemistry and Institute of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
³ Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan, ROC. Electronic address: rchang@mail.ndhu.edu.tw.

PMID: 24321549
DOI: 10.1016/j.bbrc.2013.11.128

Abstract

Viral replication depends on host proteins to supply energy and replication accessories for the sufficient production of viral progeny. In this study, we identified fructose-bisphosphate aldolase A as a binding partner of Japanese encephalitis virus (JEV) untranslated regions (UTRs) on the antigenome via RNA affinity capture and mass spectrometry. Direct interaction of aldolase A with JEV RNAs was confirmed by gel mobility shift assay and colocalization with active replication of double-stranded RNA in JEV-infected cells. Infection of JEV caused an increase in aldolase A expression of up to 33%. Knocking down aldolase A reduced viral translation, genome replication, and viral production significantly. Furthermore, JEV infection consumed 50% of cellular ATP, and the ATP level decreased by 70% in the aldolase A-knockdown cells. Overexpression of aldolase A in aldolase A-knockdown cells increased ATP levels significantly. Taken together, these results indicate that JEV replication requires aldolase A and consumes ATP. This is the first report of direct involvement of a host metabolic enzyme, aldolase A protein, in JEV replication.

Keywords: ALDOA; Fructose-bisphosphate aldolase A; JEV.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / biosynthesis*
Encephalitis Virus, Japanese / physiology*
Fructose-Bisphosphate Aldolase / antagonists & inhibitors*
Fructose-Bisphosphate Aldolase / metabolism*
HEK293 Cells
Humans
Virus Replication

Substances

Adenosine Triphosphate
Fructose-Bisphosphate Aldolase