The emergence and diversification of panzootic H5N1 influenza viruses

•A review on the ecology and evolution of H5N1 viruses is presented.•We describe the emergence of H5N1 viruses in southern China.•Trace the genomic diversification of the virus through reassortment with wild bird viruses.•Describe the virus ecology in the poultry production system in China and the use of vaccines and their impact on H5N1 evolution.•Discuss the potential for pandemic emergence of H5N1 virus.

The Asian highly pathogenic avian influenza H5N1 virus was first detected in the goose population of Guangdong, China in 1996. The viruses in this lineage are unique in their ecological success, demonstrating an extremely broad host range and becoming established in poultry over much of Asia and in Africa. H5N1 viruses have also diverged into multiple clades and subclades that generally do not cross neutralize, which has greatly confounded control measures in poultry and pre-pandemic vaccine strain selection. Although H5N1 viruses currently cannot transmit efficiently between mammals they exhibit high mortality in humans and recent experimental studies have shown that it is possible to generate an H5N1 virus that is transmissible in mammals. In addition to causing unprecedented economic losses, the long-term presence of the H5N1 virus in poultry and its frequent introductions to humans continue to pose a significant pandemic threat. Here we provide a summary of the genesis, molecular epidemiology and evolution of this H5N1 lineage, particularly the factors that have contributed to the continued diversification and ecological success of H5N1 viruses, with particular reference to the poultry production systems they have emerged from.