Pathogenesis of Influenza A/H5N1 Virus Infection in Ferrets Differs between Intranasal and Intratracheal Routes of Inoculation
Pathogenesis of Influenza A/H5N1 Virus Infection in Ferrets Differs between Intranasal and Intratracheal Routes of Inoculation
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DOI：
10.1016/j.ajpath.2011.03.026
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发表时间：
2011-07-01
影响因子：
6
通讯作者：
Kuiken, Thijs
中科院分区：
文献类型：
--
作者：
Bodewes, Rogier;Kreijtz, Joost H. C. M.;Kuiken, Thijs
大多数感染高致病性禽流感A/H5N1病毒的患者发展为严重肺炎，导致急性呼吸窘迫综合征，呼吸外疾病是一种罕见的并发症。在雪貂鼻内接种甲型流感/H5N1病毒可引起呼吸道和呼吸外器官（主要是脑）的病变。然而，传播到呼吸外器官的途径和呼吸外疾病对致病性的相对贡献在很大程度上是未知的。在本研究中，我们描述了经鼻内接种甲型流感病毒/印度尼西亚/5/2005 （H5N1）的雪貂（n = 8）呼吸道和中枢神经系统（CNS）的病变。接种后7天，8只雪貂中只有3只出现轻度或中度支气管间质性肺炎。8只雪貂均有中重度中枢神经系统病变，以脑膜脑炎、脉络膜炎和室管膜炎为特征，以脑脊液邻近组织为中心。这些结果表明，甲型流感/H5N1病毒直接从鼻腔传播到大脑，中枢神经系统病变比肺部病变对雪貂甲型流感/H5N1病毒感染的致病性贡献更大。相比之下，雪貂气管内接种同一病毒可重复引起严重的支气管间质性肺炎。在设计作为甲型流感/H5N1人感染模型的雪貂实验时，需要仔细考虑病毒接种方法。（Am J . journal, 2011, 17930-34 DOI: 10.1016/ j.j ajpath.2011.03.026）
Most patients infected with highly pathogenic avian influenza A/H5N1 virus develop severe pneumonia resulting in acute respiratory distress syndrome, with extrarespiratory disease as an uncommon complication. Intranasal inoculation of ferrets with influenza A/H5N1 virus causes lesions in both the respiratory tract and extrarespiratory organs (primarily brain). However, the route of spread to extrarespiratory organs and the relative contribution of extrarespiratory disease to pathogenicity are largely unknown. In the present study, we characterized lesions in the respiratory tract and central nervous system (CNS) of ferrets (n = 8) inoculated intranasally with influenza virus A/Indonesia/5/2005 (H5N1). By 7 days after inoculation, only 3 of 8 ferrets had a mild or moderate bronchointerstitial pneumonia. In contrast, all 8 ferrets had moderate or severe CNS lesions, characterized by meningoencephalitis, choroiditis, and ependymitis, and centered on tissues adjoining the cerebrospinal fluid. These findings indicate that influenza A/H5N1 virus spread directly from nasal cavity to brain, and that CNS lesions contributed more than pulmonary lesions to the pathogenicity of influenza A/H5N1 virus infection in ferrets. In comparison, intratracheal inoculation of ferrets with the same virus reproducibly caused severe bronchointerstitial pneumonia. The method of virus inoculation requires careful consideration in the design of ferret experiments as a model for influenza A/H5N1 in humans. (Am J Patbol 2011, 17930-34 DOI: 10.1016/j.ajpath.2011.03.026)