Increases in hemaglutinin (HA) sugar chains may contribute to the survival of influenza viruses among humans? *
Since it emerged in 1968, the human influenza A virus H3N2 subtype (so-called Hong Kong type) has undergone repeated antigenic mutations with resulting epidemics. As well, the number of sugar chains (oligosaccharides) in the globular region of hemagglutinin (HA) has gradually increased. It has been speculated that this increase in oligosaccharides may have contributed to the survival of this virus among humans. This could be because the sugar chains cover the major antigenic site of HA and so the virus escapes any attack form the host's immune system. However this concept has not been examined experimentally. The present study investigated this concept by reverse genetics and experimental infections in mice. The glycosylation sites of HA of A/Okayama/06/01 were removed by mutagenesis retrospective deconstruction, one after another. Through reverse genetics, mutant viruses were generated. Mice were intranasally infected with the original (H3-0) and mutant viruses in which the 1 to 3 glycosylation sites were removed (named H3-1, H3-2 and H3-3, respectively). One month after infection, sera were collected from infected mice and the cross reactivity of the neutralizing antibodies in the sera were assayed using various combinations of sera and viruses. H3-1 and H3-2 were highly cross-reactive, whereas H3-0 and H3-3 were clearly distinguished from H3-1 and H3-2, respectively. Both the addition and the deletion of a glycosylation site reduced cross reactivity. The present study indicated that oligosaccharides may be convenient tools for modifying immunogenicity, thereby helping an escape from immune recognition. This report also discussed an influenza epidemic pattern in New York City from this point of view. (Accepted on October 5, 2009)
