Alphacoronavirus Protein 7 Modulates Host Innate Immune Response
Alphacoronavirus Protein 7 Modulates Host Innate Immune Response
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DOI：
10.1128/jvi.01032-13
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发表时间：
2013-09-01
影响因子：
5.4
通讯作者：
Zuniga, Sonia
中科院分区：
文献类型：
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作者：
Cruz, Jazmina L. G.;Becares, Martina;Zuniga, Sonia
先天性免疫应答是抗病毒防御的第一道防线，在大多数情况下，能清除病原体且临床后果极小。病毒已发展出多种策略来破坏宿主防御机制并提高自身存活率。以传染性胃肠炎病毒（TGEV）为模型，我们先前曾报道，附属基因7通过与蛋白磷酸酶1的催化亚基（PP1c）结合来抵消宿主的抗病毒应答。在本研究中，通过转录组分析进一步分析了感染期间基因7缺失对宿主细胞的影响。将感染缺乏基因7表达的重组突变型TGEV（rTGEV - Δ7）的细胞的基因表达模式与感染亲本病毒（rTGEV - wt）的细胞的基因表达模式进行了比较。在缺乏基因7的TGEV感染期间，参与免疫应答、干扰素应答和炎症的基因上调。在体外和体内均观察到感染rTGEV - Δ7病毒期间先天性免疫应答加剧。与感染亲本病毒的细胞相比，观察到感染rTGEV - Δ7病毒的肺组织中巨噬细胞募集和活化增加。总之，在体外和体内蛋白质7的缺失导致感染后促炎反应增加和急性组织损伤。在一种在免疫学上与人类相似的猪动物模型中，我们提供了一个新的例子，说明病毒蛋白如何抵消宿主抗病毒途径以决定感染结果和发病机制。
Innate immune response is the first line of antiviral defense resulting, in most cases, in pathogen clearance with minimal clinical consequences. Viruses have developed diverse strategies to subvert host defense mechanisms and increase their survival. In the transmissible gastroenteritis virus (TGEV) as a model, we previously reported that accessory gene 7 counteracts the host antiviral response by associating with the catalytic subunit of protein phosphatase 1 (PP1c). In the present work, the effect of the absence of gene 7 on the host cell, during infection, was further analyzed by transcriptomic analysis. The pattern of gene expression of cells infected with a recombinant mutant TGEV, lacking gene 7 expression (rTGEV-Delta 7), was compared to that of cells infected with the parental virus (rTGEV-wt). Genes involved in the immune response, the interferon response, and inflammation were upregulated during TGEV infection in the absence of gene 7. An exacerbated innate immune response during infection with rTGEV-Delta 7 virus was observed both in vitro and in vivo. An increase in macrophage recruitment and activation in lung tissues infected with rTGEV-Delta 7 virus was observed compared to cells infected with the parental virus. In summary, the absence of protein 7 both in vitro and in vivo led to increased proinflammatory responses and acute tissue damage after infection. In a porcine animal model, which is immunologically similar to humans, we present a novel example of how viral proteins counteract host antiviral pathways to determine the infection outcome and pathogenesis.