Involvement of extraneural tissues and upregulation of inducible nitric oxide synthase after experimental infection with rabies virus in BALB/c mice and LEW/SsN rats.

Pi-Hung Liao, Yung-Hsiang Hsu, Hui-Hua Yang, Ming-Hseng Wang, Li-Kuang Chen

Institute of Medical Sciences, Department of Pathology, Tzu Chi University, Hualien, Taiwan.

Pathology international 2012 Sep

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Rabies virus can cause fatal encephalomyelitis, but the involvement of extraneural organs has not been well characterized. In this study, we investigated the histopathological changes and the distribution of viral antigens in extraneural organs after pathogenic rabies virus infection in mouse and rat models. In histopathological examination, classical viral encephalitis and rabies-specific Negri body were observed in the brain. In addition to the central nervous system (CNS), inflammatory responses were found in other organs, such as the heart, kidney, liver, and lung. Similarly, immunohistochemical staining and reverse transcription-polymerase chain reaction revealed the presence of rabies virus in the CNS and extraneural tissues. Moreover, macrophages, especially in the lung and heart, were involved in the infection. Transcriptional analyses of the expression of inducible nitric oxide synthase (iNOS) demonstrated that rabies virus potentiated the gene expression of iNOS in the brain, lung, and heart. The immunoreactive iNOS-positive macrophages were detected adjacent to the infection. These results suggest that macrophages are involved in the extraneural infection and the expression of iNOS in macrophages contributes to the formation of tissue inflammation. Our study indicates the involvement of extraneural organs following rabies virus infection, which may aggravate the progression of this deadly disease. © 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

Citation

Pi-Hung Liao, Yung-Hsiang Hsu, Hui-Hua Yang, Ming-Hseng Wang, Li-Kuang Chen. Involvement of extraneural tissues and upregulation of inducible nitric oxide synthase after experimental infection with rabies virus in BALB/c mice and LEW/SsN rats. Pathology international. 2012 Sep;62(9):619-27