Prototype foamy virus downregulates RelB expression to facilitate viral replication.
Prototype foamy virus downregulates RelB expression to facilitate viral replication.
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原型泡沫病毒下调 RelB 表达以促进病毒复制
DOI：
10.1002/2211-5463.12968
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发表时间：
2020-10
期刊：
影响因子：
2.6
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Zhang J;Wang C;Tuo X;Chai K;Xu Y;Qiao W;Tan J
泡沫病毒（foamy viruses，FV）是介于正逆转录病毒亚科（Orthoretrovirinae）和嗜肝DNA病毒科（Hepadnaviridae）之间的一种差距病毒。FV对体外培养的细胞具有强烈的致细胞病变作用。然而，它们在宿主中建立终身潜伏感染而没有明显的病理学。细胞因子在FV复制中的作用知之甚少。为了更好地了解这一领域，我们确定了HT 1080细胞感染原型泡沫病毒（PFV）的转录组，以测量PFV感染对细胞基因表达的影响。我们发现，作为核因子-κB（NF-κB）蛋白家族成员的RelB mRNA的水平由于PFV感染而显著降低，并且这进一步被真实的-time PCR证实。有趣的是，RelB的过表达减少了PFV的复制，而其使用小干扰RNA的消耗增加了PFV的复制。RelB的这种抑制作用是由于病毒Tas蛋白对病毒长末端重复序列（LTR）启动子和内部启动子（IP）的反式激活减弱所致。总之，这些数据表明，PFV感染下调病毒抑制宿主因子RelB，否则限制病毒基因表达。
Foamy viruses (FVs) are classified in the subfamily Spumaretrovirinae and bridge the gap between Orthoretrovirinae and Hepadnaviridae. FVs have strong cytopathic effects against cells cultured in vitro. However, they establish lifelong latent infections without evident pathology in the host. The roles of cellular factors in FV replication are poorly understood. To better understand this area, we determined the transcriptomes of HT1080 cells infected with prototype foamy virus (PFV) to measure the effect of PFV infection on the expression of cellular genes. We found that the level of RelB mRNA, a member of the nuclear factor‐κB (NF‐κB) protein family, was significantly decreased as a result of PFV infection, and this was further confirmed with real‐time PCR. Interestingly, overexpression of RelB reduced PFV replication, whereas its depletion using small interfering RNA increased PFV replication. This inhibitory effect of RelB results from diminished transactivation of the viral long terminal repeat (LTR) promoter and an internal promoter (IP) by viral Tas protein. Together, these data demonstrate that PFV infection downregulates the viral inhibitory host factor RelB, which otherwise restricts viral gene expression.
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