Positive selection pressure on the B/C domains of the E2-gene of classical swine fever virus in endemic areas under C-strain vaccination

Positive selection pressure on the B/C domains of the E2-gene of classical swine fever virus in endemic areas under C-strain vaccination
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DOI:
10.1016/j.meegid.2012.04.030
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发表时间:
2012-10-01
影响因子:
3.2
通讯作者:
Ganges, Llilianne
Ganges, Llilianne
中科院分区:
医学3区
文献类型:
--
作者:
Josue Perez, Lester;Diaz de Arce, Heidy;Ganges, Llilianne

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在古巴,尽管实施了疫苗接种计划,但猪瘟(CSF)已成为一种地方病,每年都会爆发几次疫情。有趣的是,在过去的几年里,在动物中观察到了疾病表现较轻的趋势。本研究旨在探讨猪瘟病毒(classical swine fever virus,CSFV)E2部分基因的正选择压力,以了解常规免疫条件下CSFV在猪群中的毒力机制和进化驱动力。进行选择压力分析以检测作用于特定谱系以及CSFV核苷酸序列的E2-B/C结构域的位点之间的正选择,在先前的研究中报道,并且在本工作中,使用PAML 4.3的CODEML模块中可用的几个模型。此外,在一项实验性感染试验中评估了一种代表性古巴CSF分离株的临床毒力,以扩大对猪群中流行的CSF病毒的了解。在本研究中测序的病毒基因组被分组在基因型1.2内的一个定义的簇中,正如先前对古巴CSF病毒的报道。选择压力分析没有发现沿着任何分支的正选择(dN/dS> 1)的证据。正选择压力分析估计出E2部分基因上有6个新的正选择位点。此外,CSF病的临床表现主要与疾病的轻度病程有关。大量的阳性选择位点表明,这些变化可能与病毒逃避宿主免疫应答有关。这些观察结果突出了逃逸病毒变异体与病毒毒力和致病机制中观察到的改变之间的可能关联。因此,虽然疫苗接种计划没有导致基因型变化,但毒力的改变被认为是可能的。(c)2012爱思唯尔有限公司版权所有。
In Cuba, classical swine fever (CSF) has become an endemic disease with several outbreaks each year, despite the implemented vaccination program. Interestingly, a trend towards a milder presentation of the disease has been observed among the animals during the last years. This study aimed to assess positive selection pressure acting on partial E2 gene of CSF viruses to gain insights into the mechanisms governing virulence and the driving forces of classical swine fever virus (CSFV) evolution in swine populations under regular vaccination. Selection pressure analysis were performed to detect positive selection acting on a particular lineage as well as among sites of the E2-B/C-domain of CSFV nucleotide sequences, reported in a previous study and in the present work, several models, available in the CODEML module of PAML 4.3, were used. In addition, a representative Cuban CSF isolate was assessed in an experimental infection trial for their clinical virulence in order to expand the knowledge regarding CSF viruses circulating in pig populations. The viral genomes sequenced in this study were grouped in a defined cluster within the genotype 1.2, as it has been reported previously for Cuban CSF viruses. The selection pressure analysis didn't find evidence of positive selection (dN/dS of > 1) along any branch. The positive selective pressure analysis estimated six new sites under positive selection on E2 partial gene analysed. Besides, the clinical manifestations of the CSF-disease were related mainly to a mild course of the illness. The high number of positively selected sites suggests that these changes could be associated to viral evasion of the host-immune response. These observations highlight a possible association between escape viral variants and the alterations observed in the virulence and pathogenesis of the virus. Therefore, while the vaccination programs have not led to a genotype change, alterations in virulence were suggested to arise. (c) 2012 Elsevier B.V. All rights reserved.