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Valine, the branched-chain amino acid, suppresses hepatitis C virus RNA replication but promotes infectious particle formation.

Abstract：

BACKGROUND & AIMS:Concentrations of the branched-chain amino acid (BCAA) in the serum of patients with liver cirrhosis correlate with their liver function. Oral administration of BCAA can ameliorate hypoalbuminemia and hepatic encephalopathy. In this study, we aim to clarify the role of BCAA in regulating the replication of the hepatitis C virus (HCV). METHODS:HCV sub-genomic replicon cells, genome-length replicon cells, and cells infected with cell culture-infectious HCV (HCVcc) were cultured in media supplemented with various concentrations of BCAA, followed by evaluation of the replicon or HCV abundance. RESULTS:BCAA was capable of suppressing the HCV replicon in a dose-dependent manner and the effect was independent of the mTOR pathway. Of the three BCAAs, valine was identified as being responsible for suppressing the HCV replicon. Surprisingly, an abundance of HJ3-5(YH/QL), an HCVcc, in Huh7 cells was augmented by BCAA supplementation. In contrast, BCAA suppressed an abundance of HJ3-5(wild), an HCVcc that cannot assemble virus particle in Huh7 cells. Internal ribosome entry site of HCV was shown to be a target of BCAA. Single-cycle virus production assays using Huh7-25 cells, which lacked CD81 expression, revealed that BCAA, especially valine, promoted infectious virus particle formation with minimal effect on virus secretion. Thus, BCAA was found to have two opposing effects on HCV production: suppression of the HCV genome RNA replication and promotion of infectious virus formation. CONCLUSIONS:BCAA accelerates HCV production through promotion of infectious virus formation in infected cells despite its suppressive effect on HCV genome replication.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Ishida H,Kato T,Takehana K,Tatsumi T,Hosui A,Nawa T,Kodama T,Shimizu S,Hikita H,Hiramatsu N,Kanto T,Hayashi N,Takehara T

doi

10.1016/j.bbrc.2013.06.051

subject

Has Abstract

pub_date

2013-07-19 00:00:00

pages

127-33

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)01038-3

journal_volume

437

pub_type

杂志文章

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Valine, the branched-chain amino acid, suppresses hepatitis C virus RNA replication but promotes infectious particle formation.