Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals
Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals
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DOI：
10.1128/jvi.79.18.11788-11800.2005
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Tumpey, TM
中科院分区：
文献类型：
--
作者：
Maines, TR;Lu, XH;Tumpey, TM
2003年和2004年，高致病性禽流感H5 N1病毒在亚洲各地传播，摧毁了家禽种群，导致迄今为止人类中最大和最致命的H5 N1病毒爆发。为了更好地了解在这次动物流行事件中分离的H5 N1病毒在哺乳动物中引起疾病的潜力，我们使用小鼠和雪貂模型来评估代表多个遗传和地理群体的选定的2003年和2004年H5 N1病毒的相对毒力，并将其与早期从人类分离的H5 N1毒株进行比较。自1997年以来，五个人类分离株中有四个对小鼠和雪貂都具有高度致死性，并且对雪貂的毒力水平远远高于从人类分离的其他H5 N1病毒。一个人类分离株和所有四个禽类分离株被发现在任一动物中的毒力较低。这种高毒性病毒在小鼠和雪貂呼吸道中复制到高滴度，并扩散到包括大脑在内的多个器官。雪貂的快速疾病进展和高致死率将高毒性的2004年H5 N1病毒与1997年H5 N1病毒区分开来。从同一名患者身上分离出的一对病毒有8个氨基酸的差异，包括PB 2的627处的Lys/Glu差异，先前被鉴定为小鼠中的H5 N1毒力因子。在PB 2的627处具有Glu的病毒在小鼠中仅表现出毒力的适度降低，并且在雪貂中具有高毒力，这表明对于该病毒对，K627 E PB 2差异对小鼠或雪貂中的毒力没有普遍影响。我们的研究结果表明，在评估2003年和2004年H5 N1病毒的毒力方面，小鼠和雪貂模型具有一般等效性。然而，2004年这些病毒在人类中的毒力明显增强，在雪貂中得到了更好的反映。
The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.