Rigatti Lora H, Toptan Tuna, Newsome Joseph T, Moore Patrick S, Chang Yuan
Division of Laboratory Animal Resources, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
mSphere. 2016 Dec 21;1(6). doi: 10.1128/mSphere.00334-16. eCollection 2016 Nov-Dec.
Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.
多瘤病毒(PyVs)已知可感染多种脊椎动物和无脊椎动物,并与多种疾病相关,包括癌症,尤其是在免疫抑制宿主中。从患有X连锁严重联合免疫缺陷的大鼠繁殖群体中鉴定出一种新型多瘤病毒,命名为大鼠多瘤病毒2(RatPyV2)。使用人类泛多瘤病毒免疫组织化学检测(P-PIT),最初在一个群体成员的腮腺唾液腺中检测到RatPyV2。利用来自哈德氏腺和腮腺的DNA进行滚环扩增,鉴定出一种新的5.1 kb多瘤病毒基因组,它与人类华盛顿大学(WU)和卡罗林斯卡学院(KI)多瘤病毒以及田鼠多瘤病毒密切相关,但与PyV1(RnorPyV1;也称为RatPyV1)明显不同。进一步筛查显示,12只大鼠中有12只(100%)的肺上皮细胞以及其他呼吸、生殖和腺组织中存在RatPyV2包涵体感染。尽管P-PIT是为检测与已知人类多瘤病毒相关的疾病而开发的,但在大鼠中鉴定出一种新的多瘤病毒表明,它可能作为一种广泛的筛查工具,用于检测新的以及已知的多瘤病毒。我们的研究结果表明,RatPyV2可能是实验大鼠的一种共生感染,可导致T细胞免疫缺陷大鼠发生播散性疾病。用RatPyV2感染X-SCID大鼠是移植临床前研究中合并感染发病机制和治疗选择的潜在模型。