Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus
Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus
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DOI：
10.1016/j.ajpath.2013.10.004
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发表时间：
2014-01-01
影响因子：
6
通讯作者：
Kohara, Michinori
中科院分区：
文献类型：
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作者：
Ogiwara, Haru;Yasui, Fumihiko;Kohara, Michinori
感染高致病性H5N1型禽流感病毒（H5N1 HPAIV）的患者表现为弥漫性肺泡损伤。然而，病毒感染后组织损伤和修复的时间进展仍然不清楚。因此，我们评估了经鼻感染H5N1 HPAIV或H1N1 2009大流行性流感病毒（H1N1 pdm）后小鼠肺部的序列组织病理学特征。我们通过免疫组化染色和原位杂交确定病毒在肺中的数量和定位。免疫组化使用了针对病毒蛋白的抗体和针对巨噬细胞、II型肺细胞或增殖细胞核抗原的特异性抗体。原位杂交使用RNA探针对编码核蛋白和血凝素蛋白的病毒RNA和mRNA进行检测。在多种肺细胞类型中观察到H5N1 HPAIV感染和复制，并可能导致肺损伤的快速进展。H5N1 HPAIV感染后，II型肺细胞和巨噬细胞均出现增殖。然而，大量的巨噬细胞未能阻断病毒的攻击，II型肺细胞的增殖也未能恢复受损的肺泡。相比之下，感染H1N1 pdm的小鼠表现出II型肺细胞和巨噬细胞的适度增殖和轻微的肺泡损伤。这些结果表明，H5N1型HPAIV的毒力来自于病毒广泛的细胞趋向性、病毒过度复制和弥漫性肺泡损伤的快速发展。
Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the Lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage.