Division of Infection and Immunity, University College London, London, WC1E 6BT, UK.
Department of Microbiology, New York University, New York, NY, 10016, USA.
Nat Commun. 2018 Mar 21;9(1):1167. doi: 10.1038/s41467-018-03569-2.
Varicella-zoster virus (VZV), an alphaherpesvirus, establishes lifelong latent infection in the neurons of >90% humans worldwide, reactivating in one-third to cause shingles, debilitating pain and stroke. How VZV maintains latency remains unclear. Here, using ultra-deep virus-enriched RNA sequencing of latently infected human trigeminal ganglia (TG), we demonstrate the consistent expression of a spliced VZV mRNA, antisense to VZV open reading frame 61 (ORF61). The spliced VZV latency-associated transcript (VLT) is expressed in human TG neurons and encodes a protein with late kinetics in productively infected cells in vitro and in shingles skin lesions. Whereas multiple alternatively spliced VLT isoforms (VLT) are expressed during lytic infection, a single unique VLT isoform, which specifically suppresses ORF61 gene expression in co-transfected cells, predominates in latently VZV-infected human TG. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency.
水痘-带状疱疹病毒（VZV）是一种α疱疹病毒，它在全球 >90%的人类神经元中建立终身潜伏感染，三分之一的人会复发导致带状疱疹，引发衰弱性疼痛和中风。VZV 如何维持潜伏状态尚不清楚。在这里，我们使用超深度富含病毒的 RNA 测序对潜伏感染的人三叉神经节（TG）进行研究，证明了剪接的 VZV mRNA 的一致表达，该 mRNA 与 VZV 开放阅读框 61（ORF61）反义。剪接的 VZV 潜伏相关转录物（VLT）在人 TG 神经元中表达，并在体外和带状疱疹皮肤损伤中感染细胞的晚期表达一种具有迟发动力学的蛋白质。虽然在裂解感染期间表达多种剪接的 VLT 异构体（VLT），但在潜伏感染的人 TG 中，特异性抑制共转染细胞中 ORF61 基因表达的单一独特的 VLT 异构体占优势。VLT 的发现将 VZV 与其他更好地描述的人类和动物嗜神经α疱疹病毒联系起来，并为 VZV 潜伏提供了新的见解。
