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PMID: 8289354 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sequence specificity of furin, a proprotein-processing endoprotease, for the hemagglutinin of a virulent avian influenza virus.

Journal of virology ·Vol. 68 ·No. 2 ·1994-02-00 ·Pages 1213-8

Walker JA, Molloy SS, Thomas G, Sakaguchi T, Yoshida T, Chambers TM, Kawaoka Y

Abstract

The virulence of avian influenza viruses correlates with the sensitivity of their hemagglutinin (HA) to cellular proteases. Furin, a proprotein-processing subtilisin-related endoprotease, is a leading candidate for the enzyme that cleaves the HA of virulent avian viruses. We therefore compared the specificity of furin with those of proteases in a variety of cultured cells and in a rat Golgi fraction, using the HA cleavage mutants of a virulent avian influenza virus, A/Turkey/Ireland/1378/85 (H5N8). The results indicated similar sequence specificities among the endoproteases when purified furin was used. In experiments with the vaccinia virus expression system, overexpressed furin cleaved mutant HAs that were not recognized by the endogenous proteases, resulting in an apparent broader specificity of furin. These findings authenticate the proposed role of furin as an HA-activating protease in vivo and caution against the use of expression vectors to study protease sequence specificity.

MeSH Terms
Amino Acid Sequence Animals Cells, Cultured Furin Golgi Apparatus/enzymology Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral/metabolism Influenza A virus/metabolism Liver/enzymology Molecular Sequence Data Protein Precursors/metabolism Protein Processing, Post-Translational Rats Recombinant Proteins/biosynthesis Substrate Specificity Subtilisins/genetics,metabolism
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral Protein Precursors Recombinant Proteins Subtilisins Furin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Walker J A
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Molloy S S
Thomas G
Sakaguchi T
Yoshida T
Chambers T M
Kawaoka Y
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.2.1213-1218.1994
Published
1994-02-00
Pages
1213-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC236564
Subset
IM
Grants
NIAID NIH HHS · AI-29599 · United States
NIDDK NIH HHS · DK-37274 · United States
NIDDK NIH HHS · DK-44629 · United States
External Links
PubMed source DOI: 10.1128/JVI.68.2.1213-1218.1994 PMC Full Text View journal details
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