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雪貂系统性冠状病毒在α-1 抗胰蛋白酶敲除雪貂中的感染。

Ferret Systemic Coronavirus in Alpha-1 Antitrypsin Knockout Ferrets.

机构信息

Animal Resources Program, University of Alabama at Birmingham, Birmingham, Alabama.

School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

出版信息

Comp Med. 2022 Dec 1;72(6):410-415. doi: 10.30802/AALAS-CM-22-000035. Epub 2022 Sep 14.

DOI:10.30802/AALAS-CM-22-000035
PMID:36104147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9827607/
Abstract

Ferret systemic coronavirus (FRSCV) causes a highly fatal disease of ferrets (). It is believed to be a mutated variant of ferret enteric coronavirus (FRECV) and has a clinical presentation similar to that of feline infectious peritonitis virus (FIPV) in cats. The interplay of infectious diseases and host genetics will become a greater issue in the research environment as genetically modified species other than rodents become available due to advances in gene editing technology. In this case series, we present the clinical and histopathologic features of a FRSCV outbreak that affected 5 out of 10 ferrets with α-1 antitrypsin knockout (AAT KO) over an approximately 1-y period. Clinical features varied, with the affected ferrets presenting with some combination of wasting, hind limb paralysis, incontinence or sudden death. Multiple ferrets had gross pathologic lesions consistent with FRSCV, but the lesions were typically mild. Microscopic pyogranulomatous inflammation was present in 4 ferrets. Immunohistochemistry using an anti-feline coronavirus antibody that cross reacts with ferret coronavirus confirmed infection of intralesional macrophages in 4 out of 5 animals with suspected FRSCV infection. PCR testing of formalin fixed tissue was negative for all ferrets. PCR testing of feces from healthy wild-type ferrets indicated that the endemic presence of FRECV genotype 2, while PCR surveillance testing of other in-house AAT KO ferrets revealed both enteric coronavirus genotypes 1 and 2. This case series highlights the potential for greater disease incidence in the future as genetically modified ferrets are used more often, and may support exclusion of FRECV and similar viruses from highly susceptible ferret genotypes.

摘要

雪貂系统性冠状病毒(FRSCV)可引起雪貂高度致命的疾病()。据信,它是雪貂肠冠状病毒(FRECV)的突变变体,其临床表现与猫传染性腹膜炎病毒(FIPV)相似。随着基因编辑技术的进步,除啮齿动物以外的其他基因改造物种变得可用,传染病和宿主遗传学的相互作用将成为研究环境中的一个更大问题。在本病例系列中,我们介绍了在大约 1 年的时间内,5 只α-1 抗胰蛋白酶敲除(AAT KO)雪貂中有 4 只受到 FRSCV 爆发的影响,其临床和组织病理学特征。临床特征各不相同,受影响的雪貂表现出消瘦、后肢瘫痪、失禁或突然死亡的某种组合。多只雪貂具有与 FRSCV 一致的大体病理病变,但病变通常较轻。4 只雪貂有化脓性肉芽肿性炎症。使用与雪貂冠状病毒交叉反应的抗猫冠状病毒抗体进行免疫组织化学检查,确认了 5 只疑似 FRSCV 感染动物中有 4 只动物的病灶内巨噬细胞感染。所有雪貂的福尔马林固定组织 PCR 检测均为阴性。来自健康野生型雪貂的粪便 PCR 检测表明 FRECV 基因型 2 的流行存在,而对其他内部 AAT KO 雪貂的 PCR 监测检测则表明存在肠冠状病毒基因型 1 和 2。本病例系列强调了随着基因改造雪貂的使用越来越多,未来疾病发病率可能会更高,并且可能支持从高度易感的雪貂基因型中排除 FRECV 和类似病毒。

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