Varicella-zoster virus infection of human dorsal root ganglia in vivo
Varicella-zoster virus infection of human dorsal root ganglia in vivo
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DOI：
10.1073/pnas.0501045102
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发表时间：
2005-05-03
影响因子：
11.1
通讯作者：
Arvin, AM
中科院分区：
文献类型：
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作者：
Zerboni, L;Ku, CC;Arvin, AM
水痘带状疱疹病毒（VZV）引起水痘，并在感觉神经节建立潜伏期。VZV再激活导致带状疱疹。我们建立了严重联合免疫缺陷（SCID）小鼠背根神经节（DRG）异种移植模型，研究VZV对分化神经元和卫星细胞的体内感染。DRG移植于肾被膜下，在典型的DRG结构中包含神经元和卫星细胞。VZV临床分离株感染DRG内神经元。感染后14 d，电镜观察到神经元细胞核和细胞质中可见VZ病毒粒子，卫星细胞中未见VZ病毒粒子。VZV基因组拷贝数为每10(5)个细胞7.1 × 10(7) ~ 8.0 × 10(8)个拷贝，恢复了传染性病毒。病毒复制的初始阶段在4-8周内过渡到VZV潜伏期，其特征是没有传染性病毒释放，病毒粒子组装停止，VZV基因组拷贝量减少到每10(5)个细胞3.7 x 10(5)到4.7 x 10(6)。VZV在DRG中的持续存在不需要VZV特异性适应性免疫，并且与ORF63调节基因的持续转录有关。水痘减毒活疫苗病毒表现出与临床分离株相同的短期复制、病毒DNA的持久性和显著的ORF63转录模式。VZV感染的T细胞将病毒从循环转移到DRG，表明VZV的嗜淋巴性促进了其嗜神经性。DRG异种移植可能有助于研究其他人类病毒的神经致病机制。
Varicella-zoster virus (VZV) causes varicella and establishes latency in sensory ganglia. VZV reactivation results in herpes zoster. We developed a model using human dorsal root ganglion (DRG) xenografts in severe combined immunodeficient (SCID) mice to investigate VZV infection of differentiated neurons and satellite cells in vivo. DRG engrafted under the kidney capsule and contained neurons and satellite cells within a typical DRG architecture. VZV clinical isolates infected the neurons within DRG. At 14 days postinfection, VZ virions were detected by electron microscopy in neuronal cell nuclei and cytoplasm but not in satellite cells. The VZV genome copy number was 7.1 X 10(7) to 8.0 x 10(8) copies per 10(5) cells, and infectious virus was recovered. This initial phase of viral replication was followed within 4-8 weeks by a transition to VZV latency, characterized by the absence of infectious virus release, the cessation of virion assembly, and a reduction in VZV genome copies to 3.7 x 10(5) to 4.7 x 10(6) per 10(5) cells. VZV persistence in DRG was achieved without any requirement for VZV-specific adaptive immunity and was associated with continued transcription of the ORF63 regulatory gene. The live attenuated varicella vaccine virus exhibited the same pattern of short-term replication, persistence of viral DNA, and prominent ORF63 transcription as the clinical isolates. VZV-infected T cells transferred virus from the circulation into DRG, suggesting that VZV lymphotropism facilitates its neurotropism. DRG xenografts may be useful for investigating neuropathogenic mechanisms of other human viruses.