title: Inhibition of aldolase A blocks biogenesis of ATP and attenuates Japanese encephalitis virus production.
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.
authors: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
authors: Chih-Feng
authors: CF
authors: Tien
authors: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
authors: Shih-Ching
authors: SC
authors: Cheng
authors: Department of Chemistry and Institute of Chemistry, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
authors: Yen-Peng
authors: YP
authors: Ho
authors: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
authors: Yi-Shiuan
authors: YS
authors: Chen
authors: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
authors: Jung-Hsin
authors: JH
authors: Hsu
authors: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan, ROC. Electronic address: rchang@mail.ndhu.edu.tw.
authors: Ruey-Yi
authors: RY
authors: Chang
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D004664:Encephalitis Virus, Japanese / Q000502:physiology*; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D014779:Virus Replication
chemical_list: D000255:Adenosine Triphosphate; D005634:Fructose-Bisphosphate Aldolase
keywords: ALDOA; Fructose-bisphosphate aldolase A; JEV