Investigation of varicella-zoster virus neurotropism and neurovirulence using SCID mouse-human DRG xenografts

被引:10
|
作者
Zerboni, Leigh [1 ]
Arvin, Ann [1 ,2 ]
机构
[1] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
关键词
Varicella-zoster virus; Neuropathogenesis; Neurotropism; Glycoprotein E; Glycoprotein I; SCID; DORSAL-ROOT GANGLIA; HUMAN TRIGEMINAL GANGLIA; HERPES-SIMPLEX-VIRUS; TO-CELL SPREAD; INSULIN-DEGRADING ENZYME; N-TERMINAL REGION; GLYCOPROTEIN-E; IN-VIVO; VIRAL REPLICATION; SKIN INFECTION;
D O I
10.1007/s13365-011-0066-x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Varicella-zoster virus (VZV) is a medically important human alphaherpesvirus. Investigating pathogenic mechanisms that contribute to VZV neurovirulence are made difficult by a marked host restriction. Our approach to investigating VZV neurotropism and neurovirulence has been to develop a mouse-human xenograft model in which human dorsal root ganglia (DRG) are maintained in severe compromised immunodeficient (SCID) mice. In this review, we will describe our key findings using this model in which we have demonstrated that VZV infection of SCID DRG xenograft results in rapid and efficient spread, enabled by satellite cell infection and polykaryon formation, which facilitates robust viral replication and release of infectious virus. In neurons that persist following this acute replicative phase, VZV genomes are present at low frequency with limited gene transcription and no protein synthesis, a state that resembles VZV latency in the natural human host. VZV glycoprotein I and interaction between glycoprotein I and glycoprotein E are critical for neurovirulence. Our work demonstrates that the DRG model can reveal characteristics about VZV replication and long-term persistence of latent VZV genomes in human neuronal tissues, in vivo, in an experimental system that may contribute to our knowledge of VZV neuropathogenesis.
引用
收藏
页码:570 / 577
页数:8
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