Comparative genomic analysis of five pairs of virulent parental/attenuated vaccine strains of PRRSV

Comparative genomic analysis of five pairs of virulent parental/attenuated vaccine strains of PRRSV
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五对PRRSV强毒亲本/弱毒疫苗株的比较基因组分析

DOI:
10.1016/j.vetmic.2010.11.001
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发表时间:
2011-04-21
影响因子:
3.3
通讯作者:
Tong, Guang-Zhi
Tong, Guang-Zhi
中科院分区:
农林科学2区
文献类型:
--
作者:
An, Tong-Qing;Tian, Zhi-Jun;Tong, Guang-Zhi

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猪生殖与呼吸综合征病毒(Porcine Reproductive and Respiratory Syndrome Virus,PRRSV)是猪生殖与呼吸综合征的病原体,是导致猪严重疾病的罪魁祸首,给养猪业带来了巨大的经济损失。将猪繁殖与呼吸综合征病毒(PRRSV)强毒株HuN 4在Marc-145细胞上传代112次,获得弱毒疫苗株HuN 4-F112,并测定其全基因组序列。为了了解PRRSV减毒的分子基础,我们比较和分析了HuN 4/HuN 4-F112的基因组序列,以及其他4个强毒亲本/减毒疫苗株的基因组序列。在19个PRRSV蛋白中,有两个(NSP 6和NSP 8)高度保守,没有任何突变,被认为与减毒无关。与结构蛋白相关的突变率明显高于大多数非结构蛋白。有趣的是,最小的结构蛋白E蛋白的基因在所有分析的结构基因中具有最高的突变率,并且还具有高度可变的区域。我们的研究结果表明,PRRSV减毒的决定因素是非结构基因和结构基因的多基因产物。据我们所知,这是第一个报告,表明与结构蛋白(包括E和GP 2-GP 5蛋白)可能发挥重要作用。这些结果有助于我们理解PRRSV的减毒作用,并将为进一步研究提供重要线索。(C)2010 Elsevier B. V.保留所有权利。
Porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of porcine reproductive and respiratory syndrome, is responsible for serious disease in pigs resulting in substantial economic losses in the porcine industry. An attenuated vaccine strain, HuN4-F112, was obtained by passaging virulent PRRSV strain HuN4 on Marc-145 cells (for 112 passages), and the full-genomic sequence was determined. To understand the molecular basis of attenuation of PRRSV, we compared and analyzed the genomic sequences of HuN4/HuN4-F112, together with those of other four virulent parental/attenuated vaccine strains. Among the 19 PRRSV proteins, two (NSP6 and NSP8) were highly conserved, without any mutations and considered irrelative to attenuation. The mutation rates of envelope-associated structural proteins were obviously higher than those of most non-structural proteins. It is interesting that the gene of the smallest structural protein, E protein, had the highest mutation rate among all of the structural genes analyzed, and also harbored a highly variable region. Our results indicate that determinants of PRRSV attenuation are multigenic products of both non-structural and structural genes. To our knowledge, this is the first report showing that the envelope-associated structural proteins (including E and GP2-GP5 proteins) may play a significant role. These findings contribute towards our understanding of PRRSV attenuation and will provide an important clue for further study. (C) 2010 Elsevier B.V. All rights reserved.