《Nature》：关于过去5年中国禽流感病毒的研究结果

高度致病的H5N1流感病毒（根据其关键表面蛋白的亚型“血凝素”和“神经氨酸苷酶”的英文名称第一个字母命名），是造成中国和东亚其他地方一系列禽流感爆发的原因。在泰国和越南，该病毒被证明对人类是致命的；今年2月，越南报告了该病毒在人与人之间的首例明显传播。本期Nature发表了对过去5年中国禽流感病毒的一项广泛研究的结果，结果表明，H5N1病毒继续在水生和陆生鸟中传播，并发生了广泛的基因重排。正是这些基因变化导致了一种具有显性基因型的病毒被选择，最近的人类感染也是由该病毒引起的。这样一个跨物种基因库的存在表明，要根除该病毒非常困难，也说明该病毒对东亚和其他地方的公众健康仍然是一大威胁。

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.