Pathogenesis of Frog Virus 3 (Ranavirus, Iridoviridae) Infection in Wood Frogs (Rana sylvatica)
Pathogenesis of Frog Virus 3 (Ranavirus, Iridoviridae) Infection in Wood Frogs (Rana sylvatica)
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DOI：
10.1177/0300985816684929
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发表时间：
2017-05-01
影响因子：
2.4
通讯作者：
Daoust, P. -Y.
中科院分区：
文献类型：
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作者：
Forzan, M. J.;Jones, K. M.;Daoust, P. -Y.
森林林蛙（Rana sylvatica）极易感染蛙病毒3（FV 3，Ranavirus，Iridoviridae），这是野生种群大规模死亡的原因。为了阐明FV 3感染林蛙的发病机制，将40只野生捕获的成年林蛙驯化为圈养，经口接种致死剂量为10（4.43）pfu/青蛙，并在感染后0.25，0.5，1，2，4，9和14天（dpi）安乐死。在前2 dpi期间，皮肤（瘀点）和骨髓（坏死）中零星发生轻度病变。严重病变发生在感染后1 ~ 2周，包括骨髓和髓外造血组织、脾脏和全身淋巴组织以及皮肤、粘膜和肾小管上皮细胞的坏死。感染后4天，首次在肝脏中检测到病毒DNA（聚合酶链反应）;到感染后9天和14天，检测的所有内脏（肝脏、肾脏和脾脏）、皮肤和粪便均呈阳性。免疫组织化学（IHC）首先在4 dpi时在口腔粘膜、肺和结肠中无组织学病变的小区域中检测到病毒抗原;到9和14 dpi时，在多个组织中发现与坏死相关的病毒抗原的IHC标记。根据IHC染色强度和病变严重程度，皮肤、口腔和胃肠道上皮以及肾小管上皮是病毒复制和脱落的重要部位，表明直接接触（皮肤）和粪-口污染是有效的传播途径，皮肤组织、口腔、泄殖腔拭子可能是疾病晚期（>感染后1周）的适当死前诊断样本，但在临床健康青蛙中检测感染的样本较差。
Wood frogs (Rana sylvatica) are highly susceptible to infection with Frog virus 3 (FV3, Ranavirus, Iridoviridae), a cause of mass mortality in wild populations. To elucidate the pathogenesis of FV3 infection in wood frogs, 40 wild-caught adults were acclimated to captivity, inoculated orally with a fatal dose of 10(4.43) pfu/frog, and euthanized at 0.25, 0.5, 1, 2, 4, 9, and 14 days postinfection (dpi). Mild lesions occurred sporadically in the skin (petechiae) and bone marrow (necrosis) during the first 2 dpi. Severe lesions occurred 1 to 2 weeks postinfection and consisted of necrosis of medullary and extramedullary hematopoietic tissue, lymphoid tissue in spleen and throughout the body, and epithelium of skin, mucosae, and renal tubules. Viral DNA was first detected (polymerase chain reaction) in liver at 4 dpi; by dpi 9 and 14, all viscera tested (liver, kidney, and spleen), skin, and feces were positive. Immunohistochemistry (IHC) first detected viral antigen in small areas devoid of histologic lesions in the oral mucosa, lung, and colon at 4 dpi; by 9 and 14 dpi, IHC labeling of viral antigen associated with necrosis was found in multiple tissues. Based on IHC staining intensity and lesion severity, the skin, oral, and gastrointestinal epithelium and renal tubular epithelium were important sites of viral replication and shedding, suggesting that direct contact (skin) and fecal-oral contamination are effective routes of transmission and that skin tissue, oral, and cloacal swabs may be appropriate antemortem diagnostic samples in late stages of disease (>1 week postinfection) but poor samples to detect infection in clinically healthy frogs.