Use of Highly Pathogenic Avian Influenza A(H5N1) Gain-Of-Function Studies for Molecular-Based Surveillance and Pandemic Preparedness

Zoonotic influenza viruses circulating in poultry and swinepose an ever present threat to human health. In particular, the rapid geographical expansion of highly pathogenic avian influ-enza (HPAI) A(H5N1) throughout Asia and then into Europe, the Middle East, and Africa during the 2000s galvanized the global community in an attempt to control this rapidly growing threat. Despite successful control efforts in some countries, the virus re-mains endemic in poultry in at least six countries and continues to cause human illness and deaths as well as countless outbreaks in birds. During the past decade, 668 cases and 393 deaths were de-tected and reported to the World Health Organization (WHO) (1). During the 17 years since human infections with HPAI A(H5N1) were first identified in Hong Kong, Special Administra-tive Region, People’s Republic of China, in 1997, these viruses have evolved substantially through mutation and reassortment, resulting in multiple divergent genotypes and clades (2).