Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: Enhanced virulence of Eurasian H7N7 viruses isolated from humans
Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: Enhanced virulence of Eurasian H7N7 viruses isolated from humans
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DOI：
10.1128/jvi.01235-07
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Tumpey, Terrence M.
中科院分区：
文献类型：
--
作者：
Belser, Jessica A.;Lu, Xuihua;Tumpey, Terrence M.
在2003年前，由于动物对人的直接传播或实验室事故，只有偶尔出现人感染H7流感病毒的病例报告；这些感染大多导致结膜炎。从家禽暴发和人类中分离出的甲型H7禽流感病毒增加，这引发了人们的担忧，即可能会发生更多人畜共患病，将流感病毒从家禽传播给人类。为了更好地了解H7病毒的发病机制，我们研究了它们在小鼠和雪貂模型中致病的能力。2003年分别从荷兰(荷兰/2003年)、美国东北部(2002-2003年)和加拿大(2004年)分离出高致病性和低致病性的H7病毒，对小鼠进行鼻腔感染，监测小鼠的发病率、死亡率、病毒复制和呼吸器官中促炎症细胞因子的产生。所有H7病毒都在小鼠的呼吸道中有效复制，但只有荷兰/03分离株在包括大脑在内的全身器官中复制。只有A/NL/219/03(NL/219)病毒对小鼠具有高度致死性，并可引起雪貂严重疾病。支持在感染H7亚型病毒后在人类身上观察到的明显的嗜眼性，在眼部接种后在小鼠的眼睛中检测到欧亚和北美血统的H7病毒，而从人类呼吸道分离的H7N2病毒没有检测到。因此，总的来说，H7病毒在这些动物模型中的相对毒力和细胞嗜性与在人类中观察到的毒力有关。
Before 2003, only occasional case reports of human H7 influenza virus infections occurred as a result of direct animal-to-human transmission or laboratory accidents; most of these infections resulted in conjunctivitis. An increase in isolation of avian influenza A H7 viruses from poultry outbreaks and humans has raised concerns that additional zoonotic transmissions of influenza viruses from poultry to humans may occur. To better understand the pathogenesis of H7 viruses, we have investigated their ability to cause disease in mouse and ferret models. Mice were infected intranasally with H7 viruses of high and low pathogenicity isolated from The Netherlands in 2003 (Netherlands/03), the northeastern United States in 2002-2003, and Canada in 2004 and were monitored for morbidity, mortality, viral replication, and proinflammatory cytokine production in respiratory organs. All H7 viruses replicated efficiently in the respiratory tracts of mice, but only Netherlands/03 isolates replicated in systemic organs, including the brain. Only A/NL/219/03 (NL/219), an H7N7 virus isolated from a single fatal human case, was highly lethal for mice and caused severe disease in ferrets. Supporting the apparent ocular tropism observed in humans following infection with viruses of the H7 subtype, both Eurasian and North American lineage H7 viruses were detected in the mouse eye following ocular inoculation, whereas an H7N2 virus isolated from the human respiratory tract was not. Therefore, in general, the relative virulence and cell tropism of the H7 viruses in these animal models correlated with the observed virulence in humans.