Genetic evolution of the neuraminidase of influenza A (H3N2) viruses from 1968 to 2009 and its correspondence to haemagglutinin evolution.
Each year, influenza viruses cause epidemics by evading pre-existing humoral immunity through mutations in the major glycoproteins: the haemagglutinin (HA) and the neuraminidase (NA). In 2004, the antigenic evolution of HA of human influenza A (H3N2) viruses was mapped (Smith et al., Science 305, 371-376, 2004) from its introduction in humans in 1968 until 2003. The current study focused on the genetic evolution of NA and compared it with HA using the dataset of Smith and colleagues, updated to the epidemic of the 2009/2010 season. Phylogenetic trees and genetic maps were constructed to visualize the genetic evolution of NA and HA. The results revealed multiple reassortment events over the years. Overall rates of evolutionary change were lower for NA than for HA1 at the nucleotide level. Selection pressures were estimated, revealing an abundance of negatively selected sites and sparse positively selected sites. The differences found between the evolution of NA and HA1 warrant further analysis of the evolution of NA at the phenotypic level, as has been done previously for HA.
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Kim B
KB
Westgeest
Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.|Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Miranda
M
de Graaf
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Mathieu
M
Fourment
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Theo M
TM
Bestebroer
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Ruud
R
van Beek
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Monique I J
MIJ
Spronken
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Jan C
JC
de Jong
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Guus F
GF
Rimmelzwaan
Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.|Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
Colin A
CA
Russell
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Albert D M E
ADME
Osterhaus
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Gavin J D
GJD
Smith
Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.|Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.|Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Derek J
DJ
Smith
Department of Virology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
Ron A M
RAM
Fouchier
D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D007251:Influenza, Human / Q000821:virology*; D008969:Molecular Sequence Data; D059645:Mutation Rate; D009439:Neuraminidase / Q000235:genetics*; D010802:Phylogeny; D011995:Recombination, Genetic; D012641:Selection, Genetic; D014764:Viral Proteins / Q000235:genetics*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase