Characterization of ross river virus tropism and virus-induced inflammation in a mouse model of viral arthritis and myositis
Characterization of ross river virus tropism and virus-induced inflammation in a mouse model of viral arthritis and myositis
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DOI：
10.1128/jvi.80.2.737-749.2006
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发表时间：
2006-01-01
影响因子：
5.4
通讯作者：
Heise, MT
中科院分区：
文献类型：
--
作者：
Morrison, TE;Whitmore, AC;Heise, MT
蚊媒甲型病毒是全世界人类脑炎和关节炎的重要原因。与脑炎甲型病毒不同，甲型病毒引起的关节炎的发病机制还不是很清楚。利用罗斯河病毒(RRV)病的小鼠模型，我们发现RRV的主要感染目标是近交系CD-1小鼠和成年C57BL/6J小鼠后肢的骨、关节和骨骼肌组织。此外，组织学分析表明，RRV感染导致了这些组织的严重炎症。骨骼肌组织内炎性浸润物的特征鉴定为炎性巨噬细胞、NK细胞。细胞，以及CD4(+)和CD8(+)T淋巴细胞。为了确定获得性免疫系统的作用，在缺乏功能性T和B淋巴细胞的C57BL/6J RAG-1(-/-)小鼠上检测了RRV诱导的疾病的结局。RAG-1(-/-)和野生型小鼠表现出相似的疾病症状、炎性巨噬细胞和NK细胞的浸润以及肌肉病理，提示获得性免疫反应在疾病的发生发展中不起关键作用。这些结果建立了轮状病毒病的小鼠模型，作为一种有用的系统，用于识别导致甲型病毒诱导的关节炎和肌炎的病毒和宿主因素。
Mosquito-borne alphaviruses are a significant cause of both encephalitic and arthritic disease in humans worldwide. in contrast to the encephalitic alphaviruses, the pathogenesis of alphavirus-induced arthritic disease is not well understood. Utilizing a mouse model of Ross River virus (RRV) disease, we found that the primary targets of RRV infection are bone, joint, and skeletal muscle tissues of the hind limbs in both outbred CD-1 mice and adult C57BL/6J mice. Moreover, histological analyses demonstrated that RRV infection resulted in severe inflammation of these tissues. Characterization of the inflammatory infiltrate within the skeletal muscle tissue identified inflammatory macrophages, NK. cells, and CD4(+) and CD8(+) T lymphocytes. To determine the contribution of the adaptive immune system, the outcome of RRV-induced disease was examined in C57BL/6J RAG-1(-/-) mice, which lack functional T and B lymphocytes. RAG-1(-/-) and wild-type mice developed similar disease signs, infiltration of inflammatory macrophages and NK cells, and muscle pathology, suggesting that the adaptive immune response does not play a critical role in the development of disease. These results establish the mouse model of RRV disease as a useful system for the identification of viral and host factors that contribute to alphavirus-induced arthritis and myositis.