Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004
Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004
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DOI：
10.1128/jvi.79.4.2191-2198.2005
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发表时间：
2005-02-01
影响因子：
5.4
通讯作者：
Hoffmann, E
中科院分区：
文献类型：
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作者：
Govorkova, EA;Rehg, JE;Hoffmann, E
2004年在越南和泰国爆发的H5 N1流感病毒对人类和家禽具有高度致命性;因此，新出现的A型禽流感病毒不仅对鸟类而且对人类构成持续威胁。我们在雪貂（一种很好的流感研究模型）中研究了4种人和9种禽H5 N1/04流感病毒的致病性。所有四种人分离株对鼻内接种的雪貂都是致命的。人类分离株A/Vietnam/1203/04（H5 N1）是致病性最强的分离株;疾病的严重程度与广泛的组织嗜性和多个器官（包括大脑）中的高病毒滴度相关。观察到高热、体重减轻、厌食、极度嗜睡和腹泻。两个禽类H5 N1/04分离株的致病性与人类病毒一样，可导致雪貂致命的全身感染。从禽类分离的9种H5 N1/04病毒中有7种造成轻度感染，病毒复制仅限于上呼吸道。所有鸡分离株对雪貂均无致死性。序列分析显示，所有H5 N1/04型病毒的血凝素连接肽中存在多碱基氨基酸，这表明其他基因中的多个分子差异对高水平的毒力很重要。有趣的是，人A/Vietnam/ 1203/04分离株在PB 2的627位有赖氨酸取代，并且在除M1基因外的所有基因产物中有1至8个氨基酸变化，这与A/chickenNietnam/C58/04和A/quail/Vietnam/36/04病毒不同。我们的研究结果表明，对哺乳动物致命的病毒正在亚洲的鸟类中传播，并表明雪貂（也许还有人类）的致病性反映了不同残基的复杂组合，而不是单个氨基酸的差异。
The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only to avian species but also to humans. We studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies). All four human isolates were fatal to intranasally inoculated ferrets. The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets. Seven of nine H5N1/04 viruses isolated from avian species caused mild infections, with virus replication restricted to the upper respiratory tract. All chicken isolates were nonlethal to ferrets. A sequence analysis revealed polybasic amino acids in the hemagglutinin connecting peptides of all H5N1/04 viruses, indicating that multiple molecular differences in other genes are important for a high level of virulence. Interestingly, the human A/Vietnam/ 1203/04 isolate had a lysine substitution at position 627 of PB2 and had one to eight amino acid changes in all gene products except that of the M1 gene, unlike the A/chickenNietnam/C58/04 and A/quail/Vietnam/36/04 viruses. Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference.