A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies
A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies
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DOI：
10.1177/0192623317723541
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发表时间：
2017-07-01
影响因子：
1.5
通讯作者：
Myles, Matthew
中科院分区：
文献类型：
--
作者：
Besch-Williford, Cynthia;Pesavento, Patricia;Myles, Matthew
我们报告了一种新的多瘤病毒在Prkdc和IL-2受体γ基因缺失的严重联合免疫缺陷F344大鼠中的鉴定、发病机制和传播。感染的大鼠体重减轻，繁殖力下降，死亡率下降。在呼吸道上皮、唾液和泪腺、子宫和前列腺处可观察到大量嗜碱性核内包涵体。无偏病毒基因组测序发现了一种新的多瘤病毒，暂定名为褐家鼠多瘤病毒2(Rattus Norveicus PolyomaVirus 2，RatPyV2)，与华盛顿大学(Washington University)多瘤病毒聚在一起，属于BetapolyomaVirus属的Wuki分支。原位杂交分析和定量聚合酶链式反应(PCR)结果显示，呼吸道、腺体和生殖组织上皮存在病毒核酸。多瘤病毒病在Foxn1(Rnu)裸大鼠与感染大鼠共居或实验性接种病毒后复制。在开发出RatPyV2特异性诊断方法后，一项对北美研究机构免疫能力强的老鼠的调查显示，在1000个粪便样本中，有7个样本用聚合酶链式反应检测到RatPyV2，在1500个血清样本中，有480个样本检测到抗RatPyV2抗体。这些发现表明，实验室老鼠种群中普遍存在感染，这可能对已建立的呼吸损伤模型有深远的影响。此外，RatPyV2感染的研究可能为研究人类吴氏多瘤病毒病的发病机制提供重要的系统。
We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1(rnu) nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.