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

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• 作者：Chih-Feng Tien ; Shih-Ching Cheng ; Yen-Peng Ho ; Yi-Shiuan Chen ; Jung-Hsin Hsu ; Ruey-Yi Chang
• 关键词：JEV ; Fructose-bisphosphate aldolase A ; ALDOA
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：10 January, 2014
• 年：2014
• 卷：443
• 期：2
• 页码：464-469
• 全文大小：872 K

文摘

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.