Rapid Emergence of Highly Pathogenic Avian Influenza Subtypes From a Subtype H5N1 Hemagglutinin Variant

Erik de Vries, Hongbo Guo; Meiling Dai; Peter J.M. Rottier; Frank J.M. van Kuppeveld; Cornelis A.M. de Haan


Emerging Infectious Diseases. 2015;21(5):842-846. 

In This Article

Abstract and Introduction


In 2014, novel highly pathogenic avian influenza A H5N2, H5N5, H5N6, and H5N8 viruses caused outbreaks in Asia, Europe, and North America. The H5 genes of these viruses form a monophyletic group that evolved from a clade 2.3.4 H5N1 variant. This rapid emergence of new H5Nx combinations is unprecedented in the H5N1 evolutionary history.


A highly pathogenic avian influenza (HPAI) A(H5N1) virus (A/goose/Guangdong/1/1996) was first detected in China in 1996. Multiple clades, defined by phylogenetic characterization of the H5 hemagglutinin (HA),[1] have evolved and spread across Asia, Africa, and Europe, causing enormous losses to the poultry industry. A total of 694 human infections (death rate 58%) were recorded during 2003–2014.[2]

During the evolution of HPAI H5N1 viruses, reassortment events involving the 6 internal gene segments have often been detected (reviewed in[3]), but novel subtypes (i.e., combinations of HPAI H5 with other N subtypes) have rarely been isolated. In 2014, a novel highly virulent reassortant HPAI H5N6 virus[4] caused multiple outbreaks in Southeast Asia and 1 lethal human infection, which led the Food and Agricultural Organization of the United Nations to issue a warning.[5] Outbreaks of novel HPAI H5N8 virus in South Korea,[6,7] China,[8] and Japan raised further concern, and in November 2014, this subtype emerged outside Eastern Asia, causing outbreaks in poultry farms in Germany, the Netherlands, the United Kingdom, Canada, and the United States.