Induction of apoptosis accelerates reactivation of latent HSV-1 in ganglionic organ cultures and replication in cell cultures
Induction of apoptosis accelerates reactivation of latent HSV-1 in ganglionic organ cultures and replication in cell cultures
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DOI：
10.1073/pnas.1212661109
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发表时间：
2012-09-04
影响因子：
11.1
通讯作者：
Roizman, Bernard
中科院分区：
文献类型：
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作者：
Du, Te;Zhou, Guoying;Roizman, Bernard
单纯疱疹病毒在进入体内的入口处复制，并逆行转运到感觉神经元，在那里它们可以建立一种沉默的潜伏感染，其特征是表达一种非编码潜伏相关转录物和一组microRNA。在进入体内的入口处和细胞培养物中，病毒蛋白VP 16募集细胞蛋白，其启动几种动力学类型的病毒基因的顺序去抑制。早期的研究表明，在神经节器官培养物中潜伏病毒的再激活后，所有基因立即被去阻遏，从而避免了对VP 16启动病毒基因的顺序去阻遏的需要。可以解释这些数据的一个假设是，所有类型的病毒基因的大规模再激活是细胞凋亡途径激活的结果。在这里，我们表明，两种促凋亡药物，地塞米松和2[[3-（2，3-二氯苯氧基）丙基]氨基]-乙醇，每个加速神经节器官培养中的病毒基因表达。我们还表明，在培养的细胞中，地塞米松诱导的细胞凋亡加速病毒基因表达和感染性病毒的积累。鉴于相对大量的病毒蛋白独立地阻断由病毒基因产物或外源性试剂诱导的细胞凋亡，结果是令人惊讶的。结果表明，病毒可能依赖于细胞凋亡退出潜伏期，但细胞凋亡可能是有害的病毒复制或传播的入口进入体内。
Herpes simplex viruses replicate at the portal of entry into the body and are transported retrograde to sensory neurons in which they can establish a silent, latent infection characterized by the expression of a noncoding latency-associated transcript and a set of microRNAs. At the portal of entry into the body and in cell culture a viral protein, VP16, recruits cellular proteins that initiate a sequential derepression of several kinetic classes of viral genes. Earlier studies have shown that upon reactivation of latent virus in ganglionic organ cultures all genes are derepressed at once, thus obviating the need for VP16 to initiate sequential derepression of viral genes. One hypothesis that could explain the data is that the massive reactivation of all classes of viral genes is the consequence of activation of an apoptotic pathway. Here we show that two proapoptotic drugs, dexamethasone and 2[[3-(2,3-dichlorophenoxy)propyl]amino]-ethanol, each accelerates viral gene expression in ganglionic organ cultures. We also show that in cultured cells apoptosis induced by dexamethasone accelerates viral gene expression and accumulation of infectious virus. The results are surprising in light of the relatively large number of viral proteins that independently block apoptosis induced by viral gene products or exogenous agents. The results suggest that the virus may rely on apoptosis to exit from latency but that apoptosis may be detrimental for virus replication or spread at the portal of entry into the body.