Acute murine H5N1 influenza A encephalitis.
Acute murine H5N1 influenza A encephalitis.
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DOI：
10.1111/j.1750-3639.2011.00514.x
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Wiley CA
中科院分区：
文献类型：
--
作者：
Bissel SJ;Giles BM;Wang G;Olevian DC;Ross TM;Wiley CA
甲型禽流感病毒H5N1已证实具有通过跨物种传播感染人类的能力，但迄今为止，有效的人际传播有限。在自然鸟类宿主、动物模型和散发的人类暴发中，H5N1感染与神经系统疾病有关。我们用H5N1甲型流感/越南/1203/2004感染BALB/c小鼠，研究急性脑炎期间的免疫反应。采用免疫组织化学和原位杂交技术，比较了病毒感染和免疫激活的时间过程。感染后5天，小鼠体重明显下降，需要牺牲7天。早在第1 DPI时就在肺中检测到H5N1流感，而直到第4 DPI时才观察到感染的神经元。H5N1感染BALB/c小鼠发展为严重急性全脑炎。受感染的神经元缺乏神经元周围网络的证据，并表现出凋亡的迹象。虽然肺部流感感染与早期I型干扰素反应相关，随后病毒负荷减少与IFN-γ的出现一致，但中枢神经系统环境表现出迟钝的I型干扰素反应。
Avian influenza A virus H5N1 has the proven capacity to infect humans through cross-species transmission, but to date efficient human-to-human transmission is limited. In natural avian hosts, animal models, and sporadic human outbreaks, H5N1 infection has been associated with neurological disease. We infected BALB/c mice intranasally with H5N1 influenza A/Viet Nam/1203/2004 to study the immune response during acute encephalitis. Using immunohistochemistry and in situ hybridization, we compared the time course of viral infection with activation of immunity. By 5 days post infection (DPI), mice had lost substantial body weight and required sacrifice by 7 DPI. H5N1 influenza was detected in the lung as early as 1 DPI, while infected neurons were not observed until 4 DPI. H5N1 infection of BALB/c mice developed into severe acute panencephalitis. Infected neurons lacked evidence of a perineuronal net and exhibited signs of apoptosis. While lung influenza infection was associated with an early type I interferon response followed by a reduction in viral burden concordant with appearance of IFN-γ, the CNS environment exhibited a blunted type I interferon response.
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