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经典猪瘟病毒 E2 蛋白的正选择压力驱动其毒力、发病机制和抗原性的变异:对流行地区进行流行病学监测的意义。

Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: Implication for epidemiological surveillance in endemic areas.

机构信息

Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana, Cuba.

Reiman Cancer Research Laboratory, Faculty of Medicine, University of New Brunswick, Saint John, New Brunswick, Canada.

出版信息

Transbound Emerg Dis. 2019 Nov;66(6):2362-2382. doi: 10.1111/tbed.13293. Epub 2019 Jul 24.

DOI:10.1111/tbed.13293
PMID:31306567
Abstract

Classical swine fever (CSF), caused by CSF virus (CSFV), is considered one of the most important infectious diseases with devasting consequences for the pig industry. Recent reports describe the emergence of new CSFV strains resulting from the action of positive selection pressure, due mainly to the bottleneck effect generated by ineffective vaccination. Even though a decrease in the genetic diversity of the positively selected CSFV strains has been observed by several research groups, there is little information about the effect of this selective force on the virulence degree, antigenicity and pathogenicity of this type of strains. Hence, the aim of the current study was to determine the effect of the positive selection pressure on these three parameters of CSFV strains, emerged as result of the bottleneck effects induced by improper vaccination in a CSF-endemic area. Moreover, the effect of the positively selected strains on the epidemiological surveillance system was assessed. By the combination of in vitro, in vivo and immunoinformatic approaches, we revealed that the action of the positive selection pressure induces a decrease in virulence and alteration in pathogenicity and antigenicity. However, we also noted that the evolutionary process of CSFV, especially in segregated microenvironments, could contribute to the gain-fitness event, restoring the highly virulent pattern of the circulating strains. Besides, we denoted that the presence of low virulent strains selected by bottleneck effect after inefficient vaccination can lead to a relevant challenge for the epidemiological surveillance of CSF, contributing to under-reports of the disease, favouring the perpetuation of the virus in the field. In this study, B-cell and CTL epitopes on the E2 3D-structure model were also identified. Thus, the current study provides novel and significant insights into variation in virulence, pathogenesis and antigenicity experienced by CSFV strains after the positive selection pressure effect.

摘要

古典猪瘟(Classical swine fever,CSF)由猪瘟病毒(Classical swine fever virus,CSFV)引起,被认为是对养猪业具有破坏性影响的最重要传染病之一。最近的报告描述了由于正选择压力的作用而出现的新型 CSFV 毒株,主要是由于无效疫苗接种产生的瓶颈效应。尽管几个研究小组已经观察到正选择的 CSFV 毒株的遗传多样性减少,但关于这种选择力对这种类型的毒株的毒力程度、抗原性和致病性的影响的信息很少。因此,本研究旨在确定正选择压力对在 CSF 流行地区由不当疫苗接种引起的瓶颈效应而出现的 CSFV 毒株的这三个参数的影响。此外,还评估了正选择菌株对流行病学监测系统的影响。通过体外、体内和免疫信息学方法的结合,我们揭示了正选择压力的作用会导致毒力降低以及致病性和抗原性改变。然而,我们还注意到,CSFV 的进化过程,特别是在隔离的微环境中,可能会导致获得适应性的事件,恢复循环毒株的高毒力模式。此外,我们还指出,低效疫苗接种后瓶颈效应选择的低毒力菌株的存在可能会对 CSF 的流行病学监测造成重大挑战,导致疾病报告不足,有利于病毒在野外的持续存在。在本研究中,还鉴定了 E2 3D 结构模型上的 B 细胞和 CTL 表位。因此,本研究为 CSFV 菌株在正选择压力作用后经历的毒力、发病机制和抗原性变化提供了新的重要见解。

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