Infection of Calves with Bovine Norovirus GIII.1 Strain Jena Virus: an Experimental Model To Study the Pathogenesis of Norovirus Infection
Infection of Calves with Bovine Norovirus GIII.1 Strain Jena Virus: an Experimental Model To Study the Pathogenesis of Norovirus Infection
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DOI：
10.1128/jvi.05342-11
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发表时间：
2011-11-01
影响因子：
5.4
通讯作者：
Liebler-Tenorio, Elisabeth M.
中科院分区：
文献类型：
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作者：
Otto, Peter H.;Clarke, Ian N.;Liebler-Tenorio, Elisabeth M.
以新生牛诺如病毒感染实验作为同源大动物模型，研究诺如病毒感染的发病机制并确定病毒复制的靶细胞。六头新生小牛口服接种耶拿病毒 (JV)，一种牛诺如病毒 GIII。 1株和6头小牛作为模拟接种对照。感染后，在腹泻发作前（接种后 12 小时 [hpi]）、腹泻发作后不久（18 至 21 hpi）和恢复后（接种后 4 天 [dpi]）对犊牛实施安乐死。接种JV的犊牛在接种后14～16 h出现严重水样腹泻，该症状持续53.5～67.0 h。肠道病变的特征是严重的绒毛萎缩以及绒毛上皮的损失和减弱。采用免疫组化法检测绒毛上皮细胞胞质中的病毒衣壳抗原（JV抗原）。此外，在绒毛固有层中检测到JV抗原呈阳性的颗粒物质。病变首次出现于 12 hpi，并在 18 至 19 hpi 时最为广泛，从空肠中部延伸到回肠。 4 dpi 时肠粘膜已完全恢复。没有迹象表明小鼠存在诺如病毒感染所描述的全身感染。早在感染后 12 小时，就通过逆转录 PCR (RT-PCR) 和酶联免疫吸附测定 (ELISA) 在肠内容物中发现了 JV。病毒在感染后 13 小时开始从粪便排出，并分别在感染后 23 小时或尸检时（4 dpi）停止。在整个试验过程中，通过 ELISA 或 RT-PCR 检测，没有对照犊牛的 JV 检测结果呈阳性。
The experimental infection of newborn calves with bovine norovirus was used as a homologous large animal model to study the pathogenesis of norovirus infection and to determine target cells for viral replication. Six newborn calves were inoculated orally with Jena virus (JV), a bovine norovirus GIII. 1 strain, and six calves served as mock-inoculated controls. Following infection, calves were euthanized before the onset of diarrhea (12 h postinoculation [hpi]), shortly after the onset of diarrhea (18 to 21 hpi), and postconvalescence (4 days pi [dpi]). Calves inoculated with JV developed severe watery diarrhea at 14 to 16 hpi, and this symptom lasted for 53.5 to 67.0 h. Intestinal lesions were characterized by severe villus atrophy together with loss and attenuation of villus epithelium. Viral capsid antigen (JV antigen) was detected by immunohistochemistry in the cytoplasm of epithelial cells on villi. In addition, granular material positive for JV antigen was detected in the lamina propria of villi. Lesions first appeared at 12 hpi and were most extensive at 18 to 19 hpi, extending from midjejunum to ileum. The intestinal mucosa had completely recovered at 4 dpi. There was no indication of systemic infection as described for norovirus infection in mice. JV was found in intestinal contents by reverse transcription-PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) as early as 12 hpi. Fecal shedding of the virus started at 13 hpi and stopped at 23 hpi or at necropsy (4 dpi), respectively. Throughout the trial, none of the control calves tested positive for JV by ELISA or RT-PCR.