Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia.
Many pathogens causing diarrhea do so by modulating ion transport in the gut. Respiratory pathogens are similarly associated with disturbances of fluid balance in the respiratory tract, although it is not known whether they too act by altering epithelial ion transport. Here we show that influenza virus A/PR/8/34 inhibits the amiloride-sensitive Na(+) current across mouse tracheal epithelium with a half-time of about 60 min. We further show that the inhibitory effect of the influenza virus is caused by the binding of viral hemagglutinin to a cell-surface receptor, which then activates phospholipase C and protein kinase C. Given the importance of epithelial Na(+) channels in controlling the amount of fluid in the respiratory tract, we suggest that down-regulation of Na(+) channels induced by influenza virus may play a role in the fluid transport abnormalities that are associated with influenza infections.
Departments of Physiology and Pathology, and Medical Foundation of the University of Sydney, University of Sydney, New South Wales 2006, Australia.
K
K
Kunzelmann
A H
AH
Beesley
N J
NJ
King
G
G
Karupiah
J A
JA
Young
D I
DI
Cook
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D006386:Hemagglutination Tests; D009980:Influenza A virus / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D007672:Kidney Cortex / Q000166:cytology; D007685:Kidney Tubules, Collecting / Q000166:cytology; D051379:Mice; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000502:physiology / Q000821:virology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015222:Sodium Channels; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000584:Amiloride; D002217:Carbachol; D015056:1-Methyl-3-isobutylxanthine