OCIAD1 is a host mitochondrial substrate of the hepatitis C virus NS3-4A protease

PloS One
Huong T L TranDarius Moradpour

Abstract

The hepatitis C virus (HCV) nonstructural protein 3-4A (NS3-4A) protease is a key component of the viral replication complex and the target of protease inhibitors used in current clinical practice. By cleaving and thereby inactivating selected host factors it also plays a role in the persistence and pathogenesis of hepatitis C. Here, we describe ovarian cancer immunoreactive antigen domain containing protein 1 (OCIAD1) as a novel cellular substrate of the HCV NS3-4A protease. OCIAD1 was identified by quantitative proteomics involving stable isotopic labeling using amino acids in cell culture coupled with mass spectrometry. It is a poorly characterized membrane protein believed to be involved in cancer development. OCIAD1 is cleaved by the NS3-4A protease at Cys 38, close to a predicted transmembrane segment. Cleavage was observed in heterologous expression systems, the replicon and cell culture-derived HCV systems, as well as in liver biopsies from patients with chronic hepatitis C. NS3-4A proteases from diverse hepacivirus species efficiently cleaved OCIAD1. The subcellular localization of OCIAD1 on mitochondria was not altered by NS3-4A-mediated cleavage. Interestingly, OCIAD2, a homolog of OCIAD1 with a cysteine residue in a...Continue Reading

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Citations

Aug 10, 2021·International Journal of Biological Macromolecules·Zibing YangLingbao Kong

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Datasets Mentioned

BETA
KC796090
KC411777

Methods Mentioned

BETA
biopsies
transfection
biopsy
nuclear magnetic resonance
ELISA
PCR
electrophoresis

Software Mentioned

GraphPad
ImageJ
ClustalW
GraphPad Prism
TMpred

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