These H5N1 genotype Z viruses caused extensive outbreaks in poultry and were repeatedly introduced into humans, eventually becoming endemic in poultry in Vietnam and Indonesia ( 27). One of these novel reassortants (genotype Z) became dominant in southern China since early 2002 ( 5, 22) and was subsequently transmitted to neighboring countries in East and Southeast Asia in 20 ( 22). During the same period, some of these reassortants were also detected from poultry or poultry products in Korea and Japan ( 21, 23). Many of these genotypes were first recognized during the second and third major HPAI H5N1 outbreaks in Hong Kong live-poultry markets from 2001 to 2002 ( 10, 13). Since the first detection of Gs/GD-like viruses in ducks in 2000, H5N1 viruses underwent extensive genetic reassortment, wherein many different reassortants, or genotypes, were generated ( 12, 13, 22). The precursor virus of all of these H5N1 viruses, A/goose/Guangdong/1/1996 (Gs/GD), initially became established in domestic geese in southern China from 1996 to 1999 ( 36, 39). In the past decade, the “bird flu” caused by highly pathogenic avian influenza (HPAI) H5N1 virus has developed from an endemic disease in China to a panzootic disease affecting 60 countries across Asia, Europe, and Africa ( 11). It has been 10 years since the first avian-to-human transmission of influenza virus was confirmed in Hong Kong ( 30).
Poultry trade may be responsible for virus introduction to Vietnam, while the transmission route from Hunan to Indonesia remains unclear. These results suggest a direct transmission link for H5N1 viruses between Yunnan and Vietnam and also between Hunan and Indonesia during 20. The 10 progenitor viruses were genotype Z and shared high similarity (≥99%) with their corresponding descendant viruses in most gene segments. Further phylogenetic analyses of the six internal genes showed that all 10 of those viruses maintained similar phylogenetic relationships as the surface genes. Moreover, results show that eight viruses isolated from Yunnan in 20 were most closely related to the clade 1 virus sublineage from Vietnam, Thailand, and Malaysia, while two viruses from Hunan in 20 were most closely related to viruses from Indonesia (clade 2.1). Phylogenetic analysis of the hemagglutinin and neuraminidase genes of 73 H5N1 isolates from this period revealed a greater genetic diversity in southern China than previously reported. To determine the possible source of the wave 1 H5N1 viruses, we recently conducted further sequencing and analysis of samples collected in live-poultry markets from Guangdong, Hunan, and Yunnan in southern China from 2001 to 2004. Due to the lack of influenza surveillance prior to these outbreaks, the genetic diversity and the transmission pathways of H5N1 viruses from this period remain undefined.
The transmission of highly pathogenic avian influenza H5N1 virus to Southeast Asian countries triggered the first major outbreak and transmission wave in late 2003, accelerating the pandemic threat to the world.