高度致病的H5N1流感病毒（根據(jù)其關(guān)鍵表面蛋白的亞型“血凝素”和“神經(jīng)氨酸苷酶”的英文名稱第一個字母命名）,，是造成中國和東亞其他地方一系列禽流感爆發(fā)的原因,。在泰國和越南,，該病毒被證明對人類是致命的；今年2月,，越南報告了該病毒在人與人之間的首例明顯傳播,。本期Nature發(fā)表了對過去5年中國禽流感病毒的一項廣泛研究的結(jié)果，結(jié)果表明,，H5N1病毒繼續(xù)在水生和陸生鳥中傳播,，并發(fā)生了廣泛的基因重排。正是這些基因變化導(dǎo)致了一種具有顯性基因型的病毒被選擇,，最近的人類感染也是由該病毒引起的,。這樣一個跨物種基因庫的存在表明，要根除該病毒非常困難,，也說明該病毒對東亞和其他地方的公眾健康仍然是一大威脅,。
Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia
A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 (refs 2–4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003–04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.
Figure 1 Map of China showing Hong Kong and Guangdong, Hunan and Yunnan provinces, where influenza surveillance was conducted.
Figure 3 The genotypes of H5N1 influenza virus reassortants from eastern Asia. The eight gene segments are (horizontal bars starting at the top downwards): PB2, PB1, PA, HA, NP, NA, M and NS. Each colour represents a virus lineage (red indicates origin from Gs/Gd/1/96). Genotypes (indicated by letters) were defined by gene phylogeny: a distinct phylogenetic lineage with bootstrap support 70% ( 50% for M, NP and PA genes) indicated a common origin. Genotypes A, B and C were reassortants of Gs/Gd/1/96 and one or more aquatic avian viruses. Genotype D was created when the NP gene of genotype C was replaced by that of a Dk/HK/Y280/97-like virus (H9N2 subtype). Genotype E was created when the NP gene of genotype C was replaced by that of another avian virus. Further reassortment of genotype E with other aquatic avian influenza viruses gave rise to the genotypes X0–X3, distinguished by the sources of their PB2, PA and NS genes. Genotype W differs from genotype B only in its PB2, NP and M genes. Further reassortment of genotype A or B with other aquatic avian viruses gave rise to genotypes V, Y, Z and Z+. Alternatively, genotype V may have resulted from reassortment of genotype Z with other aquatic avian viruses.
Figure 4 Phylogenetic relationships of the haemagglutinin (a) and matrix protein (b) genes of representative influenza A viruses isolated in southeastern Asia, including 2 of 6 from Indonesia, 5 of 8 from Thailand and 4 of 12 from Vietnam. Trees were generated by using maximum parsimony in the PAUP* program25 (neighbour-joining analysis with the Tamura–Nei -model, implemented in the MEGA program26, revealed the same relationships). Numbers below branches indicate bootstrap values from 1,000 replicates. Only bootstrap values that define important groups have been included owing to space constraints. Analysis was based on nucleotides 1–1012 (1,012 bp) of the HA gene and 90–945 (856 bp) of the M gene. The HA tree was rooted to A/tern/South Africa/61 and the M tree to A/equine/Prague/1/56. Scale bar, 10 nucleotide changes. Green text indicates viruses isolated from wild birds in Hong Kong; pink text indicates viruses from smuggled birds in China; and other colours show the country of origin of isolates from the late 2003 to early 2004 H5N1 outbreak. Underlined viruses have the amantadine-resistance mutation (Ser31Asn) in the M2 ion channel. Ck, chicken; Dk, duck; Gd, Guangdong; Gf, Guinea fowl; Gs, goose, HK; Hong Kong; HN, Hunan; Qa, quail; SCk, silky chicken; ST, Shantou; WDk, wild duck; YN, Yunnan.
