Mutations in the genome of the highly pathogenic porcine reproductive and respiratory syndrome virus potentially related to attenuation
Mutations in the genome of the highly pathogenic porcine reproductive and respiratory syndrome virus potentially related to attenuation
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DOI：
10.1016/j.vetmic.2011.12.012
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发表时间：
2012-05-25
影响因子：
3.3
通讯作者：
Wu, Hua
中科院分区：
文献类型：
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作者：
Leng, Xue;Li, Zhenguang;Wu, Hua
从猪繁殖与呼吸综合征(HP-PRRSV)TJ株出发，在非洲绿猴肾上皮细胞系MARC-145上传代92次，获得高致病性猪繁殖与呼吸综合征病毒(HP-PRRSV)TJM疫苗株。我们发现，从第19代开始，TJ株对仔猪的毒力大大降低。为了确定与TJM疫苗株减毒相关的突变，我们测定了Hp-PRRSV TJ病毒Marc-145传代过程中发生的核苷酸变化。TJM毒株包含360个核苷酸(120个氨基酸)缺失和118个核苷酸突变，导致48个氨基酸变化。对中间传代病毒F19、F46和F78的全序列分析表明，48株病毒中有31株(64.6%)发生在F19，7株(14.6%)发生在F46，7株(14.6%)发生在F78，3株(6.3%)发生在F92。120个氨基酸缺失发生在F19~TJM之间。因此，我们推测，分布在NSP1β、NSP2-NSP5、NSP7、NSP9、NSP10、GP4和GP5的31个氨基酸突变，以及从F19开始的NSP2区连续120个氨基酸的缺失，为观察到的弱化表型提供了强大的潜在分子基础。(C)2011爱思唯尔B.V.保留所有权利。
A live-attenuated highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS) virus (HP-PRRSV) TJM vaccine strain was derived from the HP-PRRSV TJ strain by passage 92 times in the African green monkey kidney epithelial cell line Marc-145. We found that the virulence of the TJ strain to piglets was decreased greatly from passage 19. To identify mutations associated with attenuation of the TJM vaccine strain, we determined the nucleotide changes that arose during Marc-145 passage of the HP-PRRSV TJ virus. The TJM strain contains a 360 nucleotide (120 amino acids) deletion and a 118 nucleotide mutation that resulted in 48 amino acid changes. Analysis of the complete nucleotide sequences of intermediate passage-level viruses F19, F46 and F78 showed that 31 (64.6%) of the 48 amino acid mutations occurred in F19, 7 (14.6%) occurred in F46, 7 (14.6%) occurred in F78 and 3 (6.3%) occurred in F92. The 120 amino acid deletion occurred from F19 to TJM. Therefore, we hypothesized that the 31 amino acid mutations distributed in nsp1 beta, nsp2-nsp5, nsp7, nsp9, nsp10, GP4 and GP5 and the continuous 120 amino acid deletion in the nsp2 region from F19 provide a strong potential molecular basis for the observed attenuated phenotype. (C) 2011 Elsevier B.V. All rights reserved.