TROPISM OF VARICELLA-ZOSTER VIRUS FOR HUMAN CD4(+) AND CD8(+) T-LYMPHOCYTES AND EPIDERMAL-CELLS IN SCID-HU MICE
TROPISM OF VARICELLA-ZOSTER VIRUS FOR HUMAN CD4(+) AND CD8(+) T-LYMPHOCYTES AND EPIDERMAL-CELLS IN SCID-HU MICE
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DOI：
10.1128/jvi.69.9.5236-5242.1995
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发表时间：
1995-09-01
影响因子：
5.4
通讯作者：
ARVIN, AM
中科院分区：
文献类型：
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作者：
MOFFAT, JF;STEIN, MD;ARVIN, AM
为了研究水痘带状疱疹病毒（VZV）毒株的细胞向性和致病性，我使用在肾囊下携带人胎儿胸腺/肝脏植入物或作为皮下胎儿皮肤植入物的SCiD-hu小鼠分析了VZV复制，将感染野生型VZV或用于减毒水痘疫苗的Oka毒株的MRC-5细胞注射到植入物中，通过手术取出植入物2，感染后7、14和21天，来自受感染胸腺/肝脏植入物的VZV滴度对于野生型毒株在第7天达到峰值，对于Oka毒株在第14天达到峰值，组织学分析显示以胸腺细胞耗竭和纤维化为特征的坏死区域，通过免疫组织化学染色可检测坏死区域和未显示细胞病变变化的远处区域的VZV蛋白合成，并且原位杂交检测到VZV DNA呈相同分布，感染后第7天收获的胸腺细胞荧光激活细胞分选分析显示，VZV蛋白在CD4(+)、CD8(+)和CD4(+) CD8(+) T细胞中表达； VZV 是从每个 T 细胞亚群中培养出来的，Oka 毒株对人类细胞类型具有与野生型 VZV 相似的趋向性，T 淋巴细胞释放感染性 VZV，这是关于这种高度细胞相关性病毒复制的新颖且重要的观察结果，VZV 感染的皮肤植入物表现出微观表皮病变，这些病变在组织学上与水痘的特征性病变无法区分。这些实验证明了 VZV 对人类 T 淋巴细胞，解释了其在自然疾病中引起病毒血症的能力，并证明了 SCID-hu 模型对于研究 VZV 发病机制的价值。
To investigate the cell tropism and pathogenicity of varicella-zoster virus (VZV) strains, me analyzed VZV replication by using SCiD-hu mice that carry human fetal thymus/liver implants under the kidney capsule or as subcutaneous fetal skin implants, MRC-5 cells infected with wild-type VZV or the Oka strain, used in the live attenuated varicella vaccine, were injected into the implants, The implants were surgically removed 2, 7, 14 and 21 days postinfection, The VZV titer from infected thymus/liver implants peaked on day 7 for the wild-type strain and on day 14 for the Oka strain, Histological analysis showed necrotic areas characterized by thymocyte depletion and fibrosis, VZV protein synthesis was detectable by immnnohistochemical staining in the necrotic areas and in distant regions that did not show cytopathic changes, and VZV DNA was detected by in situ hybridization in the same distribution, Fluorescence-activated cell sorting analysis of thymocytes harvested at day 7 postinfection showed that VZV proteins were expressed in CD4(+), CD8(+), and CD4(+) CD8(+) T cells; VZV was cultured from each T-cell subpopulation, The Oka strain had tropism for human cell types similar to that of wild-type VZV, T lymphocytes released infectious VZV, which is a novel and important observation about the replication of this otherwise highly cell associated virus, VZV-infected skin implants exhibited microscopic epidermal lesions that were indistinguishable histologically from the characteristic lesions of varicella, These experiments demonstrate a unique tropism of VZV for human T lymphocytes, explaining its capacity to cause viremia in natural disease, and demonstrate the value of the SCID-hu model for studies of VZV pathogenesis.