Suarez D L, Perdue M L, Cox N, Rowe T, Bender C, Huang J, Swayne D E
Southeast Poultry Research Laboratory, USDA, ARS, Athens, Georgia 30605, USA.
J Virol. 1998 Aug;72(8):6678-88. doi: 10.1128/JVI.72.8.6678-6688.1998.
Genes of an influenza A (H5N1) virus from a human in Hong Kong isolated in May 1997 were sequenced and found to be all avian-like (K. Subbarao et al., Science 279:393-395, 1998). Gene sequences of this human isolate were compared to those of a highly pathogenic chicken H5N1 influenza virus isolated from Hong Kong in April 1997. Sequence comparisons of all eight RNA segments from the two viruses show greater than 99% sequence identity between them. However, neither isolate's gene sequence was closely (>95% sequence identity) related to any other gene sequences found in the GenBank database. Phylogenetic analysis demonstrated that the nucleotide sequences of at least four of the eight RNA segments clustered with Eurasian origin avian influenza viruses. The hemagglutinin gene phylogenetic analysis also included the sequences from an additional three human and two chicken H5N1 virus isolates from Hong Kong, and the isolates separated into two closely related groups. However, no single amino acid change separated the chicken origin and human origin isolates, but they all contained multiple basic amino acids at the hemagglutinin cleavage site, which is associated with a highly pathogenic phenotype in poultry. In experimental intravenous inoculation studies with chickens, all seven viruses were highly pathogenic, killing most birds within 24 h. All infected chickens had virtually identical pathologic lesions, including moderate to severe diffuse edema and interstitial pneumonitis. Viral nucleoprotein was most frequently demonstrated in vascular endothelium, macrophages, heterophils, and cardiac myocytes. Asphyxiation from pulmonary edema and generalized cardiovascular collapse were the most likely pathogenic mechanisms responsible for illness and death. In summary, a small number of changes in hemagglutinin gene sequences defined two closely related subgroups, with both subgroups having human and chicken members, among the seven viruses examined from Hong Kong, and all seven viruses were highly pathogenic in chickens and caused similar lesions in experimental inoculations.
对1997年5月从香港一名患者体内分离出的甲型流感（H5N1）病毒的基因进行了测序，发现其基因均类似禽类基因（K. 苏巴拉奥等人，《科学》，第279卷，第393 - 395页，1998年）。将该人类分离株的基因序列与1997年4月从香港分离出的高致病性鸡H5N1流感病毒的基因序列进行了比较。对这两种病毒的所有八个RNA片段进行序列比较，结果显示它们之间的序列同一性大于99%。然而，这两种分离株的基因序列与GenBank数据库中发现的任何其他基因序列都没有密切关系（序列同一性>95%）。系统发育分析表明，八个RNA片段中至少有四个的核苷酸序列与欧亚起源的禽流感病毒聚类。血凝素基因系统发育分析还纳入了另外三个人类和两个来自香港的鸡H5N1病毒分离株的序列，这些分离株分为两个密切相关的组。然而，鸡源和人源分离株之间并没有单一的氨基酸变化将它们区分开来，但它们在血凝素裂解位点均含有多个碱性氨基酸，这与家禽的高致病性表型相关。在对鸡进行的实验性静脉接种研究中，所有七种病毒都具有高致病性，在24小时内杀死了大多数鸡。所有感染鸡都有几乎相同的病理病变，包括中度至重度弥漫性水肿和间质性肺炎。病毒核蛋白最常出现在血管内皮细胞、巨噬细胞、异嗜性粒细胞和心肌细胞中。肺水肿导致的窒息和全身性心血管衰竭是导致疾病和死亡的最可能致病机制。总之，在从香港检测的七种病毒中，血凝素基因序列的少量变化定义了两个密切相关的亚组，两个亚组都有人类和鸡的成员，并且所有七种病毒在鸡中都具有高致病性，在实验接种中引起相似的病变。
