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PMID: 8189513 Published · ppublish English Journal Article

Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins.

Journal of virology ·Vol. 68 ·No. 6 ·1994-06-00 ·Pages 3753-60

Failla C, Tomei L, De Francesco R

Abstract

The proteolytic cleavages at the NS3-NS4A, NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B junctions of hepatitis C virus (HCV) polyprotein are effected by the virus-encoded serine protease contained within NS3. Using transient expression in HeLa cells of cDNA fragments that code for regions of the HCV polyprotein, we studied whether viral functions other than NS3 are required for proteolytic processing at these sites. We found that, in addition to NS3, a C-terminal 33-amino-acid sequence of the NS4A protein is required for cleavage at the NS3-NS4A and NS4B-NS5A sites and that it accelerates the rate of cleavage at the NS5A-NS5B junction. In addition, we show that NS4A can activate the NS3 protease when supplied in trans. Our data suggest that HCV NS4A may be the functional analog of flavivirus NS2B and pestivirus p10 proteins.

MeSH Terms
Amino Acid Sequence Binding Sites Enzyme Activation HeLa Cells Hepacivirus/genetics,metabolism Humans Molecular Sequence Data Protein Precursors/genetics,metabolism Protein Processing, Post-Translational Serine Endopeptidases/metabolism Viral Nonstructural Proteins/genetics,metabolism
Chemicals
Protein Precursors Viral Nonstructural Proteins Serine Endopeptidases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Failla C
Istituto di Ricerche di Biologia Molecolare P. Angeletti-Pomezia, Rome, Italy.
Tomei L
De Francesco R
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.6.3753-3760.1994
Published
1994-06-00
Pages
3753-60
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC236880
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.68.6.3753-3760.1994 PMC Full Text View journal details
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