Divergent genetic evolution of hemagglutinin in influenza A H1N1 and A H1N2 subtypes isolated in the south-France since the winter of 2001-2002.
BACKGROUND
Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization.


OBJECTIVE
Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses.


METHODS
During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes.


RESULTS
Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity.


CONCLUSIONS
The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.
Al Faress
Shaker
S
Unite de Virologie Medicale, Laboratoire de Virologie, UMR CNRS 5537, CNR des Virus Influenza Région Sud, Domaine Rockefeller, 69373 Lyon Cedex 08, France.
Cartet
Gaëlle
G
Ferraris
Olivier
O
Norder
Helene
H
Valette
Martine
M
Lina
Bruno
B
D000818:Animals; D002460:Cell Line; D004285:Dogs; D019143:Evolution, Molecular; D005602:France; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D009980:Influenza A virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000821:virology; D010802:Phylogeny; D017422:Sequence Analysis, DNA
D019267:Hemagglutinin Glycoproteins, Influenza Virus