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埃及果蝠()中实验性马尔堡病毒感染的临床、组织病理学和免疫组织化学特征。

Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat ().

机构信息

Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA 30029, USA.

Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.

出版信息

Viruses. 2019 Mar 2;11(3):214. doi: 10.3390/v11030214.

Abstract

Egyptian rousette bats () are natural reservoir hosts of Marburg virus (MARV), and Ravn virus (RAVV; collectively called marburgviruses) and have been linked to human cases of Marburg virus disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID of Marburg virus strain Uganda 371Bat2007, a minimally passaged virus originally isolated from a wild Egyptian rousette. Control bats ( = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5⁻10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3⁻8 DPI, = 8), spleen (3⁻7 DPI, = 8), skin (inoculation site; 3⁻12 DPI, = 20), lymph nodes (3⁻10 DPI, = 6), and oral submucosa (8⁻9 DPI, = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild disease caused by a filovirus in a reservoir bat host and provide support for our experimental model of this virus-reservoir host system.

摘要

埃及果蝠()是马尔堡病毒(MARV)的天然储存宿主,拉文病毒(RAVV;统称为马尔堡病毒)与人类马尔堡病毒病(MVD)病例有关。我们通过一系列安乐死研究调查了埃及果蝠中实验性马尔堡病毒感染的临床和病理影响,发现了轻度但短暂疾病的明确证据。三组共 9 只,圈养出生的幼年雄性蝙蝠通过皮下接种 10000TCID 的马尔堡病毒株乌干达 371Bat2007 进行接种,该病毒是一种最初从野生埃及果蝠中分离的最小传代病毒。对照蝙蝠( = 3)进行模拟接种。接种后第 3、5⁻10、12 和 28 天(DPI)每天安乐死 3 只动物;对照动物在 28 DPI 安乐死。血液化学分析显示,接种后第 3、6 和 7 天丙氨酸氨基转移酶(ALT)轻度升高,具有统计学意义。接种后 9 天,淋巴细胞和单核细胞计数在接种蝙蝠中轻度升高。肝组织学显示感染蝙蝠中有小灶性炎症浸润,与先前在野生、自然感染蝙蝠中描述的病变相似。肝损伤严重程度评分在第 7 天达到高峰,与 ALT 和肝病毒 RNA 水平相关。免疫组织化学染色在肝脏(3⁻8 DPI, = 8)、脾脏(3⁻7 DPI, = 8)、皮肤(接种部位;3⁻12 DPI, = 20)、淋巴结(3⁻10 DPI, = 6)和口腔黏膜下(8⁻9 DPI, = 2)中检测到偶尔的病毒抗原。病毒抗原存在于组织细胞、肝细胞和间充质细胞中,在肝脏中,抗原染色与炎症灶共存。这些结果首次提供了在储存蝙蝠宿主中由丝状病毒引起的非常轻度疾病的明确证据,并为我们的这种病毒-宿主系统实验模型提供了支持。

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