Archives of Virology

, 156:1803 | Cite as

Identification of amino acids in highly pathogenic avian influenza H5N1 virus hemagglutinin that determine avian influenza species specificity

  • Zheng Li
  • Zhonghua Liu
  • Chi Ma
  • Linqi Zhang
  • Yuelong Su
  • George F. Gao
  • Zi Li
  • Lianxian Cui
  • Wei HeEmail author
Original Article


To test the role of neutralizing antibodies (nAbs) and receptor adaptation in interspecies transmission of influenza virus, two H5N1 strains, isolated from human and avian hosts, with four amino acid differences in hemagglutinin (HA) and seven HA mutations were studied. We found that a mutation at amino acid position 90 in the H5N1 HA, outside the receptor-binding domain (RBD), could simultaneously induce changes in the RBD conformation to escape from nAb binding and alter the receptor preference through long-range regulation. This mutation was deemed a “key event” for interspecies transmission. It is likely a result of positive selection caused by antibodies, allowing the original invasion by new species-specific variants. A mutation at amino acid position 160 in the RBD only induced a change in receptor preference. This mutation was deemed a “maintaining adaptation”, which ensured that influenza virus variants would be able to infect new organisms of a different species successfully. The mutation is the result of adaptation caused by the receptor. Our results suggest that continuing occurrence of these two types of mutations made the variants persist in the new host species.


Influenza Virus Sialic Acid Avian Influenza Avian Influenza Virus Highly Pathogenic Avian Influenza 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Highly pathogenic avian influenza




Receptor binding domain


Sialic acid



We thank Dr. Wenhui Li for his kind help in the pseudotype neutralization. This work is funded by National Institutes of Health (NIH) [grant numbers U19 AI051915-05S1].

Supplementary material

705_2011_1056_MOESM1_ESM.tif (1.4 mb)
Supplementary Fig. S1 (TIFF 1420 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Zheng Li
    • 1
  • Zhonghua Liu
    • 2
  • Chi Ma
    • 1
  • Linqi Zhang
    • 2
  • Yuelong Su
    • 3
  • George F. Gao
    • 4
  • Zi Li
    • 3
  • Lianxian Cui
    • 1
  • Wei He
    • 1
    Email author
  1. 1.The Department of Immunology, Institute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical CollegeBeijingChina
  2. 2.Center for AIDS, Institute of Pathogen BiologyChinese Academy of Medical Sciences and School of Peking Union Medical CollegeBeijingChina
  3. 3.National Influenza CenterChinese Center for Disease Control and PreventionBeijingChina
  4. 4.Center for Molecular Immunology, Institute of MicrobiologyChinese Academy of SciencesBeijingChina

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