The whole genome analysis of the wild-type and attenuated orf virus reveals that ORF022 facilitates viral replication.

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Tian Jing, Yunpeng Wang, Yukun Bu, Xi Chen, Shutong Feng, Wenbo Liu, Zhannur Niyazbekova, Dekun Chen, Xiaolong Gao, Wentao Ma
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引用次数: 0

Abstract

Background: Contagious ecthyma is an acute infectious zoonosis caused by orf virus (ORFV). Live-attenuated ORFV vaccines have played a crucial role in preventing contagious ecthyma for decades. However, these vaccines often fail to induce long-lasting immunity. In recent years, numerous ORFV genome sequences have been published, yet genomic data for attenuated strains remain limited. Furthermore, no comprehensive whole-genome-based single nucleotide polymorphisms (SNPs) analysis has been conducted to compare ORFV wild-type and attenuated strains.

Results: In this study, we performed whole-genome sequencing of ORFV wild-type and attenuated strains from Shaanxi Province. We identified two ORFV strains with genomes shorter than 130 kb, which are closely related to the SC1 attenuated strain from Sichuan Province. Additionally, we noticed that 24 genes in the attenuated strain had SNPs, with the highest number of mutations occurring in the ORF022 gene. The function of the ORF022 gene has not been previously reported. Through in vitro experiments, we demonstrated that overexpression of ORF022 enhances ORFV replication in cells. The RNA-sequencing analysis revealed that ORF022 modulates host inflammation-related signaling pathways, as evidenced by the suppression of TNF, IL-17, and Toll-like receptor signaling pathways.

Conclusions: Our findings suggest that the ORF022 in ORFV wild-type strain inhibits the host inflammatory response, reduces the immune response to ORFV, and facilitates viral replication. SNP events in attenuated strains (aFX0910) are one of the reasons for its attenuation. Investigations into the genomic sequences of attenuated viruses and the functional impact of mutated genes provide valuable insights into the mechanisms underlying ORFV attenuation and offer a foundation for the development of more effective ORFV vaccines.

野生型和减毒型口蹄疫病毒的全基因组分析表明,ORF022有利于病毒复制。
背景:传染性湿疹是由口蹄疫病毒(ORFV)引起的一种急性传染性人畜共患病。几十年来,ORFV减毒活疫苗在预防传染性湿疹方面发挥了至关重要的作用。然而,这些疫苗往往不能诱导长期免疫。近年来,已经发表了许多ORFV基因组序列,但减毒菌株的基因组数据仍然有限。此外,没有进行全面的基于全基因组的单核苷酸多态性(snp)分析来比较ORFV野生型和减毒株。结果:本研究对来自陕西省的ORFV野生型和减毒株进行了全基因组测序。结果发现,2株ORFV基因组短于130 kb,与四川产SC1减毒株亲缘关系密切。此外,我们注意到在减毒菌株中有24个基因具有snp,其中ORF022基因发生的突变数量最多。ORF022基因的功能以前没有报道过。通过体外实验,我们证明了ORF022的过表达增强了ORFV在细胞中的复制。rna测序分析显示ORF022可调节宿主炎症相关信号通路,如抑制TNF、IL-17和toll样受体信号通路。结论:ORFV野生型毒株ORF022可抑制宿主炎症反应,降低机体对ORFV的免疫应答,促进病毒复制。弱毒株(aFX0910)中的SNP事件是其衰减的原因之一。对减毒病毒的基因组序列和突变基因的功能影响的研究为了解ORFV衰减的机制提供了宝贵的见解,并为开发更有效的ORFV疫苗提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Genomics
BMC Genomics 生物-生物工程与应用微生物
CiteScore
7.40
自引率
4.50%
发文量
769
审稿时长
6.4 months
期刊介绍: BMC Genomics is an open access, peer-reviewed journal that considers articles on all aspects of genome-scale analysis, functional genomics, and proteomics. BMC Genomics is part of the BMC series which publishes subject-specific journals focused on the needs of individual research communities across all areas of biology and medicine. We offer an efficient, fair and friendly peer review service, and are committed to publishing all sound science, provided that there is some advance in knowledge presented by the work.
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