Interleukin-1β expression by a recombinant porcine reproductive and respiratory syndrome virus.
Interleukin-1β expression by a recombinant porcine reproductive and respiratory syndrome virus.
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DOI：
10.1016/j.virusres.2011.11.007
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发表时间：
2012-02
期刊：
影响因子：
5
通讯作者：
Chang KO
中科院分区：
文献类型：
--
作者：
Lawson SR;Li Y;Patton JB;Langenhorst RJ;Sun Z;Jiang Z;Christopher-Hennings J;Nelson EA;Knudsen D;Fang Y;Chang KO
构建了表达猪IL-1β的重组猪繁殖与呼吸综合征病毒（vP 129/swIL 1 β）。体外生长动力学分析表明vP 129/swIL 1 β病毒的复制速率与亲本病毒相似。vP 129/swIL 1 β病毒的体内特性表明，重组PRRSV可用作潜在的体内细胞因子递送系统。该研究为PRRS的治疗性细胞因子和基因工程疫苗的开发提供了新的途径。细胞因子白细胞介素-1 β（IL-1β）是一种有效的炎症介质，在感染的反应，并可用作免疫佐剂。本研究构建了表达猪IL-1β的重组猪繁殖与呼吸综合征病毒（vP 129/swIL 1 β）。vP 129/swIL 1 β感染MARC-145细胞36 h后，每2 × 105个细胞分泌IL-1β 1947 pg。在MARC-145细胞中的体外生长动力学分析表明vP 129/swIL 1 β病毒具有与亲本病毒相似的复制速率。我们进一步在保育猪疾病模型中对vP 129/swIL 1 β病毒进行了体内表征。感染vP 129/swIL 1 β的猪未显示出可见的临床体征，而在感染亲本病毒的猪中呼吸窘迫和嗜睡明显。荧光微球免疫分析法检测vP 129/swIL 1 β感染猪后7和14 d外周血单个核细胞IL-1β、IL-4和IFN-γ的表达水平均上调。然而，在感染vP 129/swIL 1 β或亲本病毒的猪的血清样本中未发现可检测水平的IL-1β。总之，本研究证明了重组PRRSV作为一种有用的工具来研究不同细胞因子在疾病进展和免疫应答中的作用，这代表了未来治疗应用和疫苗开发的新策略。
► A recombinant porcine reproductive and respiratory syndrome virus (vP129/swIL1β) expressing swine IL-1β was constructed. ► In vitro growth kinetics analysis showed that the vP129/swIL1β virus had a similar replication rate as that of parental virus. ► In vivo characterization of vP129/swIL1β virus demonstrated that the recombinant PRRSV can be used as a potential in vivo cytokine delivery system. ► This study represents a new approach for therapeutic cytokines and genetic engineered vaccines for controlling of PRRS. The cytokine interleukin-1 beta (IL-1β) is a potent inflammatory mediator in response to infection, and can be used as an immunological adjuvant. In this study, we constructed a recombinant porcine reproductive and respiratory syndrome virus (vP129/swIL1β) expressing swine IL-1β from the separate subgenomic mRNA inserted between the ORF1b and ORF2 genome region. MARC-145 cells infected with vP129/swIL1β secreted 1947 pg of IL-1β per 2 × 105 cells at 36 h post-infection. In vitro growth kinetics analysis in MARC-145 cells showed that the vP129/swIL1β virus had a similar replication rate as that of parental virus. We further performed in vivo characterization of the vP129/swIL1β virus in a nursery pig disease model. The vP129/swIL1β infected pigs did not show visible clinical signs, while respiratory distress and lethargy were evident in pigs infected with the parental virus. The expression of various cytokines from peripheral blood mononuclear cells measured by fluorescent microsphere immunoassay showed that IL-1β, IL-4 and IFN-γ expression levels were up-regulated in pigs infected with vP129/swIL1β at 7 and 14 days post-infection. However, no detectable level of IL-1β was found in serum samples from pigs infected with either vP129/swIL1β or parental virus. In summary, this study demonstrated a recombinant PRRSV as a useful tool to study the role of different cytokines in disease progression and immune responses, which represents a new strategy for future therapeutic application and vaccine development.
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影响因子：
5.5
作者：
Lawson, Steven;Lunney, Joan;Christopher-Hennings, Jane
通讯作者：
Christopher-Hennings, Jane
DOI：
10.1073/pnas.96.5.2367
发表时间：
1999-03-02
影响因子：
11.1
作者：
Bukreyev, A;Whitehead, SS;Collins, PL
通讯作者：
Collins, PL
影响因子：
3.7
作者：
Meier, WA;Galeota, J;Zuckermann, FA
通讯作者：
Zuckermann, FA
影响因子：
5.4
作者：
Fang, Ying;Rowland, Raymond R. R.;Nelson, Eric A.
通讯作者：
Nelson, Eric A.
影响因子：
2.4
作者：
HALBUR, PG;PAUL, PS;RATHJE, JA
通讯作者：
RATHJE, JA