Highly pathogenic avian influenza (HPAI) virus (H5N1) has appeared in >60 countries and continues to evolve and diversify at a concerning rate. Because different names have been used to describe emerging lineages of the virus, this study describes a unified nomenclature system to facilitate discussion and comparison of subtype H5N1 lineages.
The continuing geographic expansion and rapid evolution of HPAI subtype H5N1 virus across 3 continents is hindering control and eradication efforts in affected countries and raising public health concerns about a potential influenza pandemic. Since 1997, when the virus was discovered to cause disease and death in humans in Hong Kong, researchers have monitored the movement of the virus from region to region. Its molecular evolution has been characterized to better understand the spread of the virus and thus help prevent its perpetuation in poultry populations. Specific mutations and reassortment events that may enhance the virus’s ability to infect and be transmitted to humans (1–7) have also been scrutinized. Therefore, much effort has been spent to delineate the emerging lineages of the HPAI viruses (H5N1) from their earliest known progenitor, A/goose/Guangdong/96 (Gs/GD). From this ancestral virus, numerous lineages have evolved and because of rapid transcontinental spread, numerous publications have used different names to classify similar (if not identical) groups of viruses within the Gs/GD-like lineage (1–6). As a result, discussion and comparison of virus isolates have been hindered by a lack of uniformity in nomenclature, often leading to confusion in the interpretation of research results. The now routine practice of genome sequencing has also dramatically increased the sequence information available for analyses, adding to the complexity of examining the evolutionary relationships among HPAI virus (H5N1) isolates.
To address these issues, an international group of scientists and collaborators, referred to as the H5N1 Evolution Working Group, was convened at the Options for the Control of Influenza VI Conference in June 2007 in Toronto, Ontario, Canada. Their goal was to develop a unified nomenclature system for the classification of HPAI viruses (H5N1) belonging to the Gs/GD-like virus lineage. The initiative, which was encouraged and approved by 3 international agencies (the World Health Organization [WHO]), the World Organisation for Animal Health [OIE], and the Food and Agriculture Organization [FAO]), set out to unify the nomenclature system to simplify interpretation of sequence and surveillance data from different laboratories and to remove stigmatizing labeling of HPAI virus (H5N1) clades by geographic reference. Although most genes of the HPAI virus (H5N1) genome have undergone reassortment leading to their replacement by genes from lineages distinct from Gs/GD, the hemagglutinin (HA) protein gene has not been replaced since its emergence in 1996 (1). Therefore, monitoring the evolution of the Gs/GD HA lineage provides an initial constant by which H5N1 strains may be effectively compared. Taking these factors into account, we performed phylogenetic analyses on all of the publicly available subtype H5N1 HA sequences that have evolved in the Gs/GD lineage and designed a classification system. The results support the concept that the HPAI viruses (H5N1) currently circulating can be effectively grouped into multiple clades, herein designated by a hierarchical numbering system. Global adoption of the proposed H5 clade nomenclature and its expansion to other influenza lineages and genes, including other animal influenza virus subtypes, will benefit human and animal influenza research and public health.