Comparison of Monkeypox Virus Clade Kinetics and Pathology within the Prairie Dog Animal Model Using a Serial Sacrifice Study Design
Comparison of Monkeypox Virus Clade Kinetics and Pathology within the Prairie Dog Animal Model Using a Serial Sacrifice Study Design
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DOI：
10.1155/2015/965710
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Damon, Inger K.
中科院分区：
文献类型：
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作者：
Hutson, Christina L.;Carroll, Darin S.;Damon, Inger K.
草原土拨鼠猴痘病毒（MPXV）感染对研究全身性正痘病毒疾病具有重要意义。为了进一步研究MPXV分支发病机制的差异，我们在感染刚果盆地（CB）或西非（WA） MPXV后的第2、4、6、9、12、17和24天采集了28个组织，并将这些土拨鼠组鼻内感染（8 × 10(3) p.f.u）。评估样本是否存在病毒以及大体和显微镜下的病变。与WA攻毒动物相比，CB攻毒动物（第4天）从鼻黏膜、口咽淋巴结和脾脏中恢复病毒较早（第6天）。两组均在第6-9天至第17天出现原发性病毒血症（由病毒DNA显示）。与WA MPXV相比，CB MPXV传播更快，积累水平更高，并在动物中引起更高的发病率。然而，组织病理学和免疫组化（IHC）的结果是相似的。两只死于疾病的动物在所有器官中都显示出丰富的病毒抗原，除了大脑。肝脏和脾脏双免疫组化染色显示凋亡细胞（TUNEL鉴定）倾向于与痘病毒抗原共定位。有趣的是，在两个MPXV组中，脾细胞比肝细胞更常被标记为凋亡阳性。这些发现允许进一步表征MPXV分支发病机制之间的差异，包括确定早期病毒复制和细胞对病毒感染的反应中重要的位点。
Monkeypox virus (MPXV) infection of the prairie dog is valuable to studying systemic orthopoxvirus disease. To further characterize differences in MPXV clade pathogenesis, groups of prairie dogs were intranasally infected (8x10(3) p.f.u.) with Congo Basin (CB) or West African (WA) MPXV, and 28 tissues were harvested on days 2, 4, 6, 9, 12, 17, and 24 postinfection. Samples were evaluated for the presence of virus and gross and microscopic lesions. Virus was recovered from nasal mucosa, oropharyngeal lymph nodes, and spleen earlier in CB challenged animals (day 4) than WA challenged animals (day 6). For both groups, primary viremia (indicated by viral DNA) was seen on days 6-9 through day 17. CB MPXV spread more rapidly, accumulated to greater levels, and caused greater morbidity in animals compared to WA MPXV. Histopathology and immunohistochemistry (IHC) findings, however, were similar. Two animals that succumbed to disease demonstrated abundant viral antigen in all organs tested, except for brain. Dual IHC staining of select liver and spleen sections showed that apoptotic cells (identified by TUNEL) tended to colocalize with poxvirus antigen. Interestingly splenocytes were labelled positive for apoptosis more often than hepatocytes in both MPXV groups. These findings allow for further characterization of differences between MPXV clade pathogenesis, including identifying sites that are important during early viral replication and cellular response to viral infection.