Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture.
The influence on virus replication in culture of the presence and location of glycosylation sites on the haemagglutinin (HA) glycoprotein of avian influenza viruses and differences in length of the stalk region of their neuraminidase (NA) glycoprotein was examined using reassortant viruses. Plaque size was measured in the presence or absence of bacterial neuraminidase (CPNA) and/or an influenza virus NA inhibitor, zanamivir, to assess the relative contribution of the NA to replication efficiency in tissue culture. The following conclusions were drawn, (1) HA lacking glycosylation at 158 gives inefficient growth when combined with short-stalked NAs, and efficient growth when combined with long-stalked NAs. (2) Glycosylation at 158 of HA makes the virus less dependent on NA for release from its receptors. (3) HA with glycosylation at 158 gives efficient growth when combined with short-stalked NAs but, when combined with long-stalked NAs, growth is very efficient and excess NA activity is disadvantageous. (4) HA having glycosylation at 158 combined with short-stalked NAs, or HA lacking glycosylation at 158 combined with long-stalked NAs may represent optimal combinations. The results reinforce the importance of a balance of HA and NA activity for efficient virus exit from, and entry into cells.
Baigent
S J
SJ
Compton Laboratory, Division of Molecular Biology, Institute for Animal Health, Compton, Berkshire, RG20 7NN, Newbury, UK. sue.baigent@bbsrc.ac.uk
McCauley
J W
JW
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002642:Chick Embryo; D003016:Clostridium perfringens / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006031:Glycosylation; D006146:Guanidines; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009980:Influenza A virus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011714:Pyrans; D012794:Sialic Acids / Q000494:pharmacology; D010948:Viral Plaque Assay; D053243:Zanamivir
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011714:Pyrans; D012794:Sialic Acids; D009439:Neuraminidase; D053243:Zanamivir