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PMID: 2829180 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 85 ·No. 2 ·1988-01-00 ·Pages 324-8

Kawaoka Y, Webster RG

Abstract

Cleavage of the hemagglutinin (HA) in tissue culture systems has been correlated with virulence of avian influenza viruses. To examine the structural requirements for cleavage of the HA, the HA gene from a virulent H5 influenza virus was expressed in mammalian cells (CV-1), and the cleavage site of the HA was explored by using site-specific mutagenesis. The expressed HA protein exhibited normal cleavage, transport to the cell membrane, and ability to adsorb and to fuse erythrocytes at pH 5. Site-specific mutagenesis of the HA directly established that (i) most of the basic amino acids at this site are critical for cleavage activation; (ii) besides the connecting peptide sequence, at least one other structural feature of the HA is required for enzyme recognition; and (iii) the length of the connecting peptide can abrogate the structural feature(s).

MeSH Terms
Amino Acid Sequence Animals Cell Line Cloning, Molecular DNA Restriction Enzymes Hemadsorption Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral/genetics,immunology Influenza A virus/genetics,immunology,pathogenicity Plasmids Simian virus 40/genetics Species Specificity Transfection Virulence
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral DNA Restriction Enzymes
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kawaoka Y
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Webster R G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.85.2.324
Published
1988-01-00
Pages
324-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC279540
Subset
IM
Grants
NIAID NIH HHS · AI 08831 · United States
NIAID NIH HHS · AI 52586 · United States
NCI NIH HHS · CA 21765 · United States
External Links
PubMed source DOI: 10.1073/pnas.85.2.324 PMC Full Text View journal details
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