An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A

C. Failla, L. Tomei, R. De Francesco

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) genomic RNA is translated into a large polyprotein that is processed into structural and nonstructural proteins. Processing at the N termini of several nonstructural proteins requires sequences contained in both NS3 and NS4A. NS3 contains a serine protease, whereas the function of NS4A in proteolysis is yet to be determined. By using the vaccinia virus-T7 hybrid expression system to transiently express HCV polypeptides in HeLa cells, we studied the effect of several N-terminal and C-terminal deletions of HCV NS3 on the processing activity at all the downstream cleavage sites. In this way, we have delineated the minimal domain of NS3 required for the serine protease activity associated with this protein. In addition, we demonstrate the formation of a stable complex between NS3 and NS4A: analysis of the deletion mutants reveals a region at the N terminus of NS3 that is necessary for both complex formation and modulation of the proteolytic activity by NS4A but not for the NS4A-independent serine protease activity of NS3.

Original languageEnglish
Pages (from-to)1769-1777
Number of pages9
JournalJournal of Virology
Volume69
Issue number3
Publication statusPublished - 1995

Fingerprint

Hepatitis C virus
Serine Proteases
serine proteinases
Hepacivirus
proteinases
Polyproteins
Vaccinia virus
Proteins
HeLa Cells
proteolysis
Proteolysis
polypeptides
amino acid sequences
proteins
RNA
genomics
mutants
Peptides
hepatitis C virus NS3 protein
cells

ASJC Scopus subject areas

  • Immunology

Cite this

An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A. / Failla, C.; Tomei, L.; De Francesco, R.

In: Journal of Virology, Vol. 69, No. 3, 1995, p. 1769-1777.

Research output: Contribution to journalArticle

@article{11ac784bbc7c483aba61e0499dadb166,
title = "An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A",
abstract = "Hepatitis C virus (HCV) genomic RNA is translated into a large polyprotein that is processed into structural and nonstructural proteins. Processing at the N termini of several nonstructural proteins requires sequences contained in both NS3 and NS4A. NS3 contains a serine protease, whereas the function of NS4A in proteolysis is yet to be determined. By using the vaccinia virus-T7 hybrid expression system to transiently express HCV polypeptides in HeLa cells, we studied the effect of several N-terminal and C-terminal deletions of HCV NS3 on the processing activity at all the downstream cleavage sites. In this way, we have delineated the minimal domain of NS3 required for the serine protease activity associated with this protein. In addition, we demonstrate the formation of a stable complex between NS3 and NS4A: analysis of the deletion mutants reveals a region at the N terminus of NS3 that is necessary for both complex formation and modulation of the proteolytic activity by NS4A but not for the NS4A-independent serine protease activity of NS3.",
author = "C. Failla and L. Tomei and {De Francesco}, R.",
year = "1995",
language = "English",
volume = "69",
pages = "1769--1777",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A

AU - Failla, C.

AU - Tomei, L.

AU - De Francesco, R.

PY - 1995

Y1 - 1995

N2 - Hepatitis C virus (HCV) genomic RNA is translated into a large polyprotein that is processed into structural and nonstructural proteins. Processing at the N termini of several nonstructural proteins requires sequences contained in both NS3 and NS4A. NS3 contains a serine protease, whereas the function of NS4A in proteolysis is yet to be determined. By using the vaccinia virus-T7 hybrid expression system to transiently express HCV polypeptides in HeLa cells, we studied the effect of several N-terminal and C-terminal deletions of HCV NS3 on the processing activity at all the downstream cleavage sites. In this way, we have delineated the minimal domain of NS3 required for the serine protease activity associated with this protein. In addition, we demonstrate the formation of a stable complex between NS3 and NS4A: analysis of the deletion mutants reveals a region at the N terminus of NS3 that is necessary for both complex formation and modulation of the proteolytic activity by NS4A but not for the NS4A-independent serine protease activity of NS3.

AB - Hepatitis C virus (HCV) genomic RNA is translated into a large polyprotein that is processed into structural and nonstructural proteins. Processing at the N termini of several nonstructural proteins requires sequences contained in both NS3 and NS4A. NS3 contains a serine protease, whereas the function of NS4A in proteolysis is yet to be determined. By using the vaccinia virus-T7 hybrid expression system to transiently express HCV polypeptides in HeLa cells, we studied the effect of several N-terminal and C-terminal deletions of HCV NS3 on the processing activity at all the downstream cleavage sites. In this way, we have delineated the minimal domain of NS3 required for the serine protease activity associated with this protein. In addition, we demonstrate the formation of a stable complex between NS3 and NS4A: analysis of the deletion mutants reveals a region at the N terminus of NS3 that is necessary for both complex formation and modulation of the proteolytic activity by NS4A but not for the NS4A-independent serine protease activity of NS3.

UR - http://www.scopus.com/inward/record.url?scp=0028851296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028851296&partnerID=8YFLogxK

M3 - Article

VL - 69

SP - 1769

EP - 1777

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -