[Functional interactions of the influenza virus glycoproteins].
Hemagglutinin (HA) and neuraminidase (NA) are functionally related coat glycoproteins of the influenza virus (Flu). HA interacts with terminal sialyl residues of oligosaccharides and ensures the binding of the virus particle to the cell surface. NA is a receptor-destroying enzyme that removes sialyl residues from oligosaccharides contained in cell and virus components and thereby prevents aggregation of virus particles. Analysis of reasortants combining low-functional NA of human Flu with HA of avian Flu showed that sialyl residues are not completely removed in some cases. With high HA affinity for sialyl substrates, such virus particles aggregate, aggregates accumulate on the cell surface, and virus yield decreases. Serial passaging of low-yield aggregating reassortants may lead to selection of high-yield variants, which do not aggregate. A loss of aggregation is due to a decrease in HA affinity for high-molecular-weight sialyl substrates. On evidence of sequencing of the HA gene in original reassortants and their nonaggregating variants, HA affinity is reduced and aggregation lost owing to a mechanism common for different HA antigenic subtypes (H2, H3, H4, and H13). This is an increase in the negative charge as a result of an amino acid substitution in the vicinity of the receptor-binding pocket of HA. Taken together, these findings suggest a way of postreassortment adaptation which improves the functional match of HA and NA. The experimental system employed provides a model of natural processes associated with generation of Flu variants having a pandemic potential.
Rudneva
I A
IA
Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Moscow, 123098 Russia.
Il'iushina
N A
NA
Shilov
A A
AA
Varich
N L
NL
Sinitsyn
B V
BV
Kropotkina
E A
EA
Kaverin
N V
NV
D019943:Amino Acid Substitution; D000818:Animals; D001717:Birds / Q000821:virology; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D009975:Orthomyxoviridae / Q000235:genetics / Q000502:physiology*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009844:Oligosaccharides; D009439:Neuraminidase