Chisholm Susan E, Howard Keith, Gómez Mar Valés, Reyburn Hugh T
Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, United Kingdom.
J Infect Dis. 2007 Apr 15;195(8):1160-8. doi: 10.1086/512862. Epub 2007 Mar 2.
Natural killer (NK) cells are an important component of the immune response to a number of viruses; however, the molecular basis of how NK cells discriminate between healthy and virus-infected cells is largely unknown. Here, we show that expression of the immediate-early gene product ICP0 is sufficient to produce an increased susceptibility to NK lysis of herpes simplex virus (HSV)-infected cells. This effect does not depend on down-regulation of major histocompatibility complex class I molecules or on the induction of expression of ligands for the activating NKG2D receptor. Detection by NK cells of the changes in the target cell induced by HSV ICP0 gene expression depends on the natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46. To our knowledge, this is the first identification of a viral gene that triggers the up-regulation of cellular ligands for the NCR; moreover, these observations highlight the importance of the NCR for immunosurveillance of viral infection by NK cells.
自然杀伤（NK）细胞是对多种病毒免疫反应的重要组成部分；然而，NK细胞如何区分健康细胞和病毒感染细胞的分子基础在很大程度上尚不清楚。在此，我们表明即刻早期基因产物ICP0的表达足以使单纯疱疹病毒（HSV）感染的细胞对NK细胞裂解的敏感性增加。这种效应不依赖于主要组织相容性复合体I类分子的下调，也不依赖于激活型NKG2D受体配体表达的诱导。NK细胞对HSV ICP0基因表达诱导的靶细胞变化的检测依赖于自然细胞毒性受体（NCR）NKp30、NKp44和NKp46。据我们所知，这是首次鉴定出一种触发NCR细胞配体上调的病毒基因；此外，这些观察结果突出了NCR对NK细胞免疫监视病毒感染的重要性。
