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PMID: 7507186 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Influenza virus M2 protein ion channel activity stabilizes the native form of fowl plague virus hemagglutinin during intracellular transport.

Journal of virology ·Vol. 68 ·No. 2 ·1994-02-00 ·Pages 911-9

Takeuchi K, Lamb RA

Abstract

The influenza A/fowl plague virus/Rostock/34 hemagglutinin (HA), which is cleaved intracellularly and has a high pH threshold (pH 5.9) for undergoing its conformational change to the low-pH form, was expressed from cDNA in CV-1 and HeLa T4 cells in the absence of other influenza virus proteins. It was found, by biochemical assays, that the majority of the HA molecules were in a form indistinguishable from the low-pH form of HA. The acidotropic agent, ammonium chloride, stabilized the accumulation of HA in its native form. Coexpression of HA and the homotypic influenza virus M2 protein, which has ion channel activity, stabilized the accumulation of HA in its pH neutral (native) form, and the M2 protein ion channel blocker, amantadine, prevented the rescue of HA in its native form. These data provide direct evidence that the influenza virus M2 protein ion channel activity can affect the status of the conformational form of cleaved HA during intracellular transport.

MeSH Terms
Amantadine/pharmacology Ammonium Chloride/pharmacology Animals Biological Transport Cells, Cultured Chlorocebus aethiops Endopeptidases/pharmacology HeLa Cells Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral/drug effects,genetics,metabolism Hexosaminidases/pharmacology Humans Hydrogen-Ion Concentration Influenza A virus/metabolism Ion Channels Oxidation-Reduction Protein Conformation Recombinant Proteins/metabolism Viral Matrix Proteins/genetics,metabolism
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral Ion Channels M-protein, influenza virus M2 protein, Influenza A virus Recombinant Proteins Viral Matrix Proteins Ammonium Chloride Amantadine Hexosaminidases Endopeptidases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Takeuchi K
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500.
Lamb R A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1994-02-00
Pages
911-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC236528
Subset
IM
Grants
NIAID NIH HHS · AI-20201 · United States
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