Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Ion selectivity and activation of the M2 ion channel of influenza virus.
Shimbo K
,
Brassard DL
,
Lamb RA
,
Pinto LH
.
???displayArticle.abstract???
The influenza A virus-associated M2 ion channel is generally believed to function during uncoating of virions in infected cells. On endocytosis of a virion into the lumen of endosomes, the M2 ion channel is thought to cause acidification of the virion interior. In addition, the influenza virus M2 ion channel is thought to function in the exocytic pathway by equilibrating the pH gradient between the acidic lumen of the trans-Golgi network and the neutral cytoplasm. A necessary test of the proposed roles of the influenza virus M2 ion channel in the virus life cycle is to show directly that the M2 ion channel conducts protons. We have measured the ionic selectivity and activation of three subtypes (Udorn, Weybridge, and Rostock) of the M2 ion channel in oocytes of Xenopus laevis by measurement of 1) the intracellular pH (pHin) of voltage-clamped oocytes, 2) the current-voltage relationship in solutions of various pH and ionic composition, and 3) the flux of 86Rb. We took advantage of the low pHin achieved during incubation in low pH medium to study the effects of low pHin on M2 activation. Oocytes expressing each of the three subtypes of the M2 protein a) underwent a slow acidification when incubated in medium of low pH (acidification was blocked by the M2 ion channel inhibitor, amantadine); b) had current-voltage relationships that shifted to more positive values and had greater conductance when the pHout was lowered (this relationship was modified when Na- was replaced by NH4+ or Li+); c) had an amantadine-sensitive influx of Rb+. The effects on the current-voltage relationship of reduced pHin were opposed to the increased conductance found with reduced pHout. We interpret these results to indicate that the M2 ion channel is capable of conducting H+ and that other ions may also be conducted. Moreover, the channel conductance is reduced by decreased pHin. These findings are consistent with the proposed roles of the M2 protein in the life cycle of influenza A virus.
Ammann,
Neutral carrier based hydrogen ion selective microelectrode for extra- and intracellular studies.
1981, Pubmed
Ammann,
Neutral carrier based hydrogen ion selective microelectrode for extra- and intracellular studies.
1981,
Pubmed
Bland,
Cation transport in lung epithelial cells derived from fetal, newborn, and adult rabbits.
1986,
Pubmed
Bukrinskaya,
Influenza virus uncoating in infected cells and effect of rimantadine.
1982,
Pubmed
Burckhardt,
Pathways of NH3/NH4+ permeation across Xenopus laevis oocyte cell membrane.
1992,
Pubmed
,
Xenbase
Ciampor,
Evidence that the amantadine-induced, M2-mediated conversion of influenza A virus hemagglutinin to the low pH conformation occurs in an acidic trans Golgi compartment.
1992,
Pubmed
Ciampor,
Regulation of pH by the M2 protein of influenza A viruses.
1992,
Pubmed
Cicirelli,
Internal pH of Xenopus oocytes: a study of the mechanism and role of pH changes during meiotic maturation.
1983,
Pubmed
,
Xenbase
DeCoursey,
Na(+)-H+ antiport detected through hydrogen ion currents in rat alveolar epithelial cells and human neutrophils.
1994,
Pubmed
Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase
Fei,
Expression cloning of a mammalian proton-coupled oligopeptide transporter.
1994,
Pubmed
,
Xenbase
Grambas,
Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses.
1992,
Pubmed
Grambas,
Maturation of influenza A virus hemagglutinin--estimates of the pH encountered during transport and its regulation by the M2 protein.
1992,
Pubmed
Hay,
The molecular basis of the specific anti-influenza action of amantadine.
1985,
Pubmed
Helenius,
Unpacking the incoming influenza virus.
1992,
Pubmed
Holsinger,
Analysis of the posttranslational modifications of the influenza virus M2 protein.
1995,
Pubmed
,
Xenbase
Holsinger,
Influenza virus M2 integral membrane protein is a homotetramer stabilized by formation of disulfide bonds.
1991,
Pubmed
Holsinger,
Influenza A virus M2 ion channel protein: a structure-function analysis.
1994,
Pubmed
,
Xenbase
Howl,
A method for the manufacture of single barrel liquid ion-selective microelectrodes: an in situ study of ant venom pH.
1988,
Pubmed
Kemp,
Identification and properties of pathways for K+ transport in guinea-pig and rat alveolar epithelial type II cells.
1994,
Pubmed
Lamb,
Identification of a second protein (M2) encoded by RNA segment 7 of influenza virus.
1981,
Pubmed
Lamb,
Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface.
1985,
Pubmed
Marsh,
Keeping the viral coat on.
1992,
Pubmed
Martin,
Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import.
1991,
Pubmed
O'Connor,
Calcium, potassium, and sodium exchange by full-grown and maturing Xenopus laevis oocytes.
1977,
Pubmed
,
Xenbase
Pinto,
Influenza virus M2 protein has ion channel activity.
1992,
Pubmed
,
Xenbase
Schroeder,
Functional reconstitution in lipid vesicles of influenza virus M2 protein expressed by baculovirus: evidence for proton transfer activity.
1994,
Pubmed
Shimbo,
Viral and cellular small integral membrane proteins can modify ion channels endogenous to Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Skehel,
On the mechanism of inhibition of influenza virus replication by amantadine hydrochloride.
1978,
Pubmed
Skehel,
Influenza virus. Amantadine blocks the channel.
1992,
Pubmed
Sugrue,
Specific structural alteration of the influenza haemagglutinin by amantadine.
1990,
Pubmed
Sugrue,
Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel.
1991,
Pubmed
Takeuchi,
Influenza virus M2 protein ion channel activity stabilizes the native form of fowl plague virus hemagglutinin during intracellular transport.
1994,
Pubmed
Tosteson,
Reconstitution of the influenza virus M2 ion channel in lipid bilayers.
1994,
Pubmed
,
Xenbase
Wang,
Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block.
1993,
Pubmed
,
Xenbase
Wang,
Activation of the M2 ion channel of influenza virus: a role for the transmembrane domain histidine residue.
1995,
Pubmed
,
Xenbase
Wang,
Direct measurement of the influenza A virus M2 protein ion channel activity in mammalian cells.
1994,
Pubmed
Zebedee,
Influenza A virus M2 protein: monoclonal antibody restriction of virus growth and detection of M2 in virions.
1988,
Pubmed
Zebedee,
Characterization of the influenza virus M2 integral membrane protein and expression at the infected-cell surface from cloned cDNA.
1985,
Pubmed
