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Background  Since 2005, the Qinghai-like lineage of the highly pathogenic avian influenza A virus H5N1 has rapidly spread westward to Europe, the Middle East and Africa, reaching a dominant level at a global scale in 2006.    Methods  Based on a combination of genetic sequence data and H5N1 outbreak information from 2005 to 2011, we use an interdisciplinary approach to improve our understanding of the transmission pattern of this particular clade 2.2, and present cartography of global spatiotemporal transmission footprints with genetic characteristics.    Results  Four major viral transmission routes were derived with three sources— Russia, Mongolia, and the Middle East (Kuwait and Saudi Arabia)—in the three consecutive years 2005, 2006 and 2007. With spatiotemporal transmission along each route, genetic distances to isolate A/goose/Guangdong/1996 are becoming significantly larger, leading to a more challenging situation in certain regions like Korea, India, France, Germany, Nigeria and Sudan. Europe and India have had at least two incursions along multiple routes, causing a mixed virus situation. In addition, spatiotemporal distribution along the routes showed that 2007/2008 was a temporal separation point for the infection of different host species; specifically, wild birds were the main host in 2005–2007/2008 and poultry was responsible for the genetic mutation in 2009–2011. “Global-to-local” and “high-to-low latitude” transmission footprints have been observed.    Conclusions  Our results suggest that both wild birds and poultry play important roles in the transmission of the H5N1 virus clade, but with different spatial, temporal, and genetic dominance. These characteristics necessitate that special attention be paid to countries along the transmission routes.

Global spatiotemporal and genetic footprint of the H5N1 avian influenza virus