Varicella-zoster virus-infected human sensory neurons are resistant to apoptosis, yet human foreskin fibroblasts are susceptible: Evidence for a cell-type-specific apoptotic response
Varicella-zoster virus-infected human sensory neurons are resistant to apoptosis, yet human foreskin fibroblasts are susceptible: Evidence for a cell-type-specific apoptotic response
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DOI：
10.1128/jvi.77.23.12852-12864.2003
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发表时间：
2003-12-01
影响因子：
5.4
通讯作者：
Abendroth, A
中科院分区：
文献类型：
--
作者：
Hood, C;Cunningham, AL;Abendroth, A
病毒感染细胞诱导凋亡或程序性细胞死亡是宿主重要的抗病毒防御机制，一些疱疹病毒已经进化出调节凋亡的策略，以提高其存活和传播。在这项研究中，我们检测了水痘带状疱疹病毒（VZV）诱导原代人背根神经节神经元和原代人包皮成纤维细胞（HFFs）凋亡的能力。使用三种独立的方法（膜联蛋白V， TUNEL[末端脱氧核苷酸转移酶介导的dutp -生物素缺口末端标记]染色和电镜）来评估这些细胞在接种后第1,2,4天的凋亡情况。三种方法均可检测到vzv感染的hff细胞凋亡。与此形成鲜明对比的是，在产生性VZV感染的神经元中未检测到凋亡。低传代临床分离株Schenke和适应组织培养的ROka菌株均诱导HFFs细胞凋亡，但不诱导神经元细胞凋亡，这表明这种细胞类型特异性的凋亡表型不是VZV菌株特异性的。这些数据表明，在产生性VZV感染期间，HFFs和神经元对细胞凋亡的调节有显著差异。在神经元感染过程中，抑制细胞凋亡可能通过促进这些有丝分裂后细胞的存活，在潜伏感染的建立、维持和再激活中发挥重要作用。
The induction of apoptosis or programmed cell death in virus-infected cells is an important antiviral defense mechanism of the host, and some herpesviruses have evolved strategies to modulate apoptosis in order to enhance their survival and spread. In this study, we examined the ability of varicella-zoster virus (VZV) to induce apoptosis in primary human dorsal root ganglion neurons and primary human foreskin fibroblasts (HFFs). Three independent methods (annexin V, TUNEL [terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling] staining, and electron microscopy) were used to assess apoptosis in these cells on days 1, 2, and 4 postinoculation. By all three methods, apoptosis was readily detected in VZV-infected HFFs. In stark contrast, apoptosis was not detected during productive VZV infection of neurons. The low-passage clinical isolate Schenke and the tissue culture-adapted ROka strain both induced apoptosis in HFFs but not in neurons, suggesting that this cell-type-specific apoptotic phenotype was not VZV strain specific. These data show that the regulation of apoptosis differs markedly between HFFs and neurons during productive VZV infection. Inhibition of apoptosis during infection of neurons may play a significant role in the establishment, maintenance, and reactivation of latent infection by promoting survival of these postmitotic cells.