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禽腺病毒9型dUTPase在宿主免疫反应调节中发挥作用。

Fowl Aviadenovirus 9 dUTPase Plays a Role in Regulation of the Host Immune Response.

作者信息

Deng Li, Griffin Bryan D, Pei Yanlong, Leishman David, McBey Betty-Anne, Sharif Shayan, Nagy Éva

机构信息

Department of Pathobiology, Ontario Veterinary College, University of Guelph , Guelph, Canada .

出版信息

Viral Immunol. 2017 Nov;30(9):662-670. doi: 10.1089/vim.2017.0068. Epub 2017 Sep 25.

Abstract

Fowl aviadenoviruses (FAdVs) are distributed worldwide in poultry farms. Some FAdVs are the causative agents of inclusion body hepatitis and hydropericardium syndrome that cause significant economic losses to the poultry industry. In contrast with human adenovirus, the study of the molecular biology of FAdV is still far behind. We previously showed that FAdV-9 open reading frame 1 (ORF1) is a dUTPase enzyme that contributes to the upregulation of type I interferons and is not required for virus replication in vitro. In the present study, we compared virus replication in vivo and the host immune response in chickens orally inoculated with a dUTPase knockout virus (ORF1stop), the rescued version of ORF1stop (resORF1), and wtFAdV-9. Our data showed that replication of ORF1stop was delayed on days 1 and 3 postinoculation compared with wtFAdV-9, as evidenced by significantly less virus shedding in feces and lower viral loads in tissues. Moreover, we found that there was a significant difference in the induction of cytokine gene mRNA expression in tissues and IgG antibody responses in ORF1stop versus wtFAdV-9-infected chickens, suggesting that ORF1 plays some roles in modulating the host immune response. Our study provides useful data on the mechanism of the host immune response against FAdV infection.

摘要

禽腺病毒(FAdVs)在世界各地的家禽养殖场中均有分布。一些FAdVs是包涵体肝炎和心包积水综合征的病原体,给家禽业造成了重大经济损失。与人类腺病毒相比,FAdV分子生物学的研究仍远远落后。我们之前表明,FAdV-9开放阅读框1(ORF1)是一种dUTPase酶,有助于上调I型干扰素,并且在体外病毒复制过程中并非必需。在本研究中,我们比较了口服接种dUTPase敲除病毒(ORF1stop)、ORF1stop的拯救版本(resORF1)和野生型FAdV-9的鸡体内的病毒复制情况以及宿主免疫反应。我们的数据表明,与野生型FAdV-9相比,接种后第1天和第3天ORF1stop的复制延迟,粪便中病毒排出量显著减少以及组织中病毒载量降低可证明这一点。此外,我们发现,在ORF1stop感染的鸡与野生型FAdV-9感染的鸡之间,组织中细胞因子基因mRNA表达的诱导和IgG抗体反应存在显著差异,这表明ORF1在调节宿主免疫反应中发挥了一些作用。我们的研究为宿主针对FAdV感染的免疫反应机制提供了有用的数据。

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