Lusso P, Malnati M S, Garzino-Demo A, Crowley R W, Long E O, Gallo R C
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Nature. 1993 Apr 1;362(6419):458-62. doi: 10.1038/362458a0.
Natural killer (NK) cells are a functionally defined subset of non-T, non-B lymphocytes of bone marrow origin, which induce lysis of selected target cells, including neoplastic and virus-infected cells. The NK cell function provides an important mechanism of primary defence against viruses in vivo, as demonstrated by the occurrence of multiple herpesvirus infections in patients congenitally lacking NK cells. Here we show that functionally competent CD3- NK clones can be productively infected by human herpesvirus 6 (HHV-6), a T-lymphotropic DNA virus that may play a role in the acquired immunodeficiency syndrome (AIDS) and in the chronic fatigue syndrome, two disorders associated with a defective NK cell activity. The infection is cytopathic and induces de novo expression of CD4, an antigen not expressed within the NK lineage, thereby predisposing NK cells to infection by human immunodeficiency virus type 1 (HIV-1). These results provide evidence that a herpesvirus can directly target and kill NK cells, a potential strategy to suppress the natural anti-viral immunity of the host.
自然杀伤（NK）细胞是一类功能明确的、起源于骨髓的非T、非B淋巴细胞亚群，可诱导特定靶细胞发生裂解，这些靶细胞包括肿瘤细胞和病毒感染细胞。NK细胞功能为体内抵御病毒提供了重要的初级防御机制，先天性缺乏NK细胞的患者发生多种疱疹病毒感染即证明了这一点。在此我们表明，功能正常的CD3-NK克隆可被人疱疹病毒6型（HHV-6）有效感染，HHV-6是一种嗜T淋巴细胞DNA病毒，可能在获得性免疫缺陷综合征（AIDS）和慢性疲劳综合征中起作用，这两种疾病都与NK细胞活性缺陷有关。这种感染具有细胞病变效应，并诱导CD4从头表达，CD4是一种在NK细胞谱系中不表达的抗原，从而使NK细胞易受1型人类免疫缺陷病毒（HIV-1）感染。这些结果证明疱疹病毒可直接靶向并杀死NK细胞，这是一种抑制宿主天然抗病毒免疫的潜在策略。
