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通过P-PIT检测在一群X-SCID大鼠中鉴定和表征新型大鼠多瘤病毒2

Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay.

作者信息

Rigatti Lora H, Toptan Tuna, Newsome Joseph T, Moore Patrick S, Chang Yuan

机构信息

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.

出版信息

mSphere. 2016 Dec 21;1(6). doi: 10.1128/mSphere.00334-16. eCollection 2016 Nov-Dec.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb46/5177731/af23d9f01f7f/sph0061622120001.jpg

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