New evidence suggests Southern China as a common source of multiple clusters of highly pathogenic H5N1 avian influenza virus.

Highly pathogenic H5N1 avian influenza is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A global effort is underway to control or eradicate the highly pathogenic H5N1 avian influenza virus in poultry and prevent human exposure, both of which may also reduce the risk of pandemic emergence. Hemagglutinin gene sequences from 215 human H5N1 influenza viruses were used to trace the source and dispersal pattern of human H5N1 influenza viruses on a global scale. A mutation network and phylogenetic analyses of the hemagglutinin gene show that human H5N1 influenza viruses can be clearly divided among 4 clusters across geographic space. On the basis of analysis of the N-glycosylation sites at positions 100 and 170 in the hemagglutinin protein, human H5N1 influenza viruses were also divided into 3 types. When we combined these analyses with geographic information system data analyses, we found that Southern China is often a common source of multiple clusters of H5N1 influenza viruses and that each cluster has different dispersal patterns and individual evolutionary features. In summary, the genetic evidence presented here provides clear evidence for multiple clusters of human H5N1 influenza viruses that initially originated in Southern China.

[1]  H. Bandelt,et al.  Median-joining networks for inferring intraspecific phylogenies. , 1999, Molecular biology and evolution.

[2]  Y. Kawaoka,et al.  Properties and Dissemination of H5N1 Viruses Isolated during an Influenza Outbreak in Migratory Waterfowl in Western China , 2006, Journal of Virology.

[3]  Yi Guan,et al.  Three Indonesian clusters of H5N1 virus infection in 2005. , 2006, The New England journal of medicine.

[4]  Y. Guan,et al.  Changing Epidemiology and Ecology of Highly Pathogenic Avian H5N1 Influenza Viruses , 2007, Avian diseases.

[5]  Xiu-Feng Wan,et al.  Evolution of Highly Pathogenic H5N1 Avian Influenza Viruses in Vietnam between 2001 and 2007 , 2008, PloS one.

[6]  Justin T Fowler,et al.  Avian influenza frequently asked questions. , 2004, Releve epidemiologique hebdomadaire.

[7]  Y. Guan,et al.  Avian flu: H5N1 virus outbreak in migratory waterfowl , 2005, Nature.

[8]  N. Blom,et al.  Prediction of post‐translational glycosylation and phosphorylation of proteins from the amino acid sequence , 2004, Proteomics.

[9]  Ming Liao,et al.  Characterization of a highly pathogenic H5N1 influenza virus derived from bar-headed geese in China. , 2006, The Journal of general virology.

[10]  R. Webster,et al.  H5N1 influenza--continuing evolution and spread. , 2006, The New England journal of medicine.

[11]  Manuel C. Peitsch,et al.  SWISS-MODEL: an automated protein homology-modeling server , 2003, Nucleic Acids Res..

[12]  R. Lathrop,et al.  A statistical phylogeography of influenza A H5N1 , 2007, Proceedings of the National Academy of Sciences.

[13]  S. Schultz-Cherry,et al.  Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses , 2000, Journal of Virology.

[14]  G. Gao,et al.  Highly Pathogenic H5N1 Influenza Virus Infection in Migratory Birds , 2005, Science.

[15]  L. Campitelli,et al.  Characterization of Low-Pathogenic H5 Subtype Influenza Viruses from Eurasia: Implications for the Origin of Highly Pathogenic H5N1 Viruses , 2007, Journal of Virology.

[16]  Oie,et al.  Toward a Unified Nomenclature System for Highly Pathogenic Avian Influenza Virus (H5N1) , 2008, Emerging infectious diseases.

[17]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[18]  Y. Shu,et al.  Human avian influenza A (H5N1) virus infection in China , 2009, Science in China Series C: Life Sciences.

[19]  Isolation of avian influenza A(H5N1) viruses from humans--Hong Kong, May-December 1997. , 1997, MMWR. Morbidity and mortality weekly report.

[20]  Sudhir Kumar,et al.  MEGA2: molecular evolutionary genetics analysis software , 2001, Bioinform..

[21]  Yi Guan,et al.  Genotypic diversity of H5N1 highly pathogenic avian influenza viruses. , 2008, The Journal of general virology.