OCIAD1 is a host mitochondrial substrate of the hepatitis C virus NS3-4A protease
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe 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 similar position and identical subcellular localization, was not cleaved by NS3-4A. Domain swapping experiments revealed that the sequence surrounding the cleavage site as well as the predicted transmembrane segment contribute to substrate selectivity. Overexpression as well as knock down and rescue experiments did not affect the HCV life cycle in vitro, raising the possibility that OCIAD1 may be involved in the pathogenesis of hepatitis C in vivo.
CitationPLoS One. 2020 Jul 22;15(7):e0236447. doi: 10.1371/journal.pone.0236447.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
SponsorsEuropean Research Council
The following license files are associated with this item:
- Creative Commons
- Quantitative proteomics identifies the membrane-associated peroxidase GPx8 as a cellular substrate of the hepatitis C virus NS3-4A protease.
- Authors: Morikawa K, Gouttenoire J, Hernandez C, Dao Thi VL, Tran HT, Lange CM, Dill MT, Heim MH, Donzé O, Penin F, Quadroni M, Moradpour D
- Issue date: 2014 Feb
- Hepacivirus NS3/4A Proteases Interfere with MAVS Signaling in both Their Cognate Animal Hosts and Humans: Implications for Zoonotic Transmission.
- Authors: Anggakusuma, Brown RJP, Banda DH, Todt D, Vieyres G, Steinmann E, Pietschmann T
- Issue date: 2016 Dec 1
- Identification of novel small molecule inhibitors against the NS3/4A protease of hepatitis C virus genotype 4a.
- Authors: El-Sayed SM, Ali MAM, El-Gendy BEM, Dandash SS, Issac Y, Saad R, Azab MM, Mohamed MR
- Issue date: 2018
- Antiviral suppression vs restoration of RIG-I signaling by hepatitis C protease and polymerase inhibitors.
- Authors: Liang Y, Ishida H, Lenz O, Lin TI, Nyanguile O, Simmen K, Pyles RB, Bourne N, Yi M, Li K, Lemon SM
- Issue date: 2008 Nov
- Extended interaction networks with HCV protease NS3-4A substrates explain the lack of adaptive capability against protease inhibitors.
- Authors: Dultz G, Shimakami T, Schneider M, Murai K, Yamane D, Marion A, Zeitler TM, Stross C, Grimm C, Richter RM, Bäumer K, Yi M, Biondi RM, Zeuzem S, Tampé R, Antes I, Lange CM, Welsch C
- Issue date: 2020 Oct 2