Infection of porcine alveolar macrophages with recombinant chimeric porcine reproductive and respiratory syndrome virus: Effects on cellular gene transcription and virus growth
Infection of porcine alveolar macrophages with recombinant chimeric porcine reproductive and respiratory syndrome virus: Effects on cellular gene transcription and virus growth
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DOI：
10.1016/j.virusres.2009.06.009
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发表时间：
2009-10-01
期刊：
影响因子：
5
通讯作者：
Risatti, Guillermo R.
中科院分区：
文献类型：
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作者：
Gudmundsdottir, Ingigerdur;Risatti, Guillermo R.
猪繁殖与呼吸综合征病毒（PRRSV）影响宿主主要靶细胞（巨噬细胞）对感染反应的遗传决定因素尚未确定。在这里，我们已经使用了重组病毒，包括ORF 1A，以确定与原代肺泡巨噬细胞（PAM）培养物中促炎和抗炎细胞因子表达的生长和调节相关的PRRSV决定因素。在体外对致病性毒株NVSL 97-7895（FL 12 v）遗传背景中包含PRRSV减毒活疫苗Prime Pac（LAV SP）ORF 1A的三个基因组嵌合体进行了表征。与亲本病毒不同，包含编码NSP 2至NSP 8的基因组区域的两种重组病毒在PAM培养物中显示出生长减少。研究了病毒感染对PAM中25种免疫调节细胞基因在感染后24和48 h（hpi）的基因激活的影响。将用重组和LAV SP病毒感染的PAM中的稳态mRNA水平与用亲本病毒FL 12 v感染的细胞中观察到的水平进行比较。重组病毒诱导的转录激活模式不同于亲本FL 12 v诱导的模式，表明PRRSV ORF 1A对PAM基因表达的调节作用。(C)2009爱思唯尔有限公司版权所有。
Porcine reproductive and respiratory syndrome virus (PRRSV) genetic determinants affecting the response of the host primary target cell, the macrophage, to infection are yet to be defined. Here we have used recombinant viruses encompassing ORF 1A to identify PRRSV determinants associated with growth and modulation of pro- and anti-inflammatory cytokine expression in primary pulmonary alveolar macrophages (PAMs) cultures. Three genomic chimeras encompassing ORF 1A of PRRSV live attenuated vaccine Prime Pac (LAV SP) in the genetic background of pathogenic strain NVSL 97-7895 (FL12v) were characterized in vitro. Unlike parental viruses, two of the recombinant viruses encompassing the area of the genome encoding for NSP2 to NSP8 showed reduced growth in PAM cultures. The effect of virus infections on gene activation was studied for 25 immunomodulatory cellular genes in PAMs at 24 and 48 h post-infection (hpi). Steady state mRNA levels in PAMs infected with recombinant and LAV SP viruses were compared to levels observed in cells infected with parental virus FL12v. Recombinant viruses induced patterns of transcriptional activation differing from patterns induced by parental FL12v, suggesting a regulatory role of PRRSV ORF1A on PAM gene expression. (C) 2009 Elsevier B.V. All rights reserved.