Effect of hemagglutinin glycosylation on influenza virus susceptibility to neuraminidase inhibitors.
Inhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA). Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication. With the use of reverse genetics technique, we investigated the effect of glycans attached at Asn 94a, 129, and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activity.
Mishin
Vasiliy P
VP
Department of Internal Medicine, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Novikov
Dmitri
D
Hayden
Frederick G
FG
Gubareva
Larisa V
LV
D000081:Acetamides / Q000494:pharmacology; D000371:Agglutination; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000821:virology; D006031:Glycosylation; D006146:Guanidines; D006388:Hemagglutinins / Q000378:metabolism*; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000502:physiology; D053139:Oseltamivir; D011714:Pyrans; D012794:Sialic Acids / Q000494:pharmacology; D053243:Zanamivir
D000081:Acetamides; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D006388:Hemagglutinins; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir