Flamand L, Stefanescu I, Menezes J
Pediatric Research Center, University of Montreal, Quebec, Canada.
J Clin Invest. 1996 Mar 15;97(6):1373-81. doi: 10.1172/JCI118557.
The marked tropism of human herpesvirus-6 (HHV-6) for natural killer (NK) cells and T lymphocytes has led us to investigate the effect of HHV-6 on cellular cytotoxicity. We describe here how HHV-6 infection of peripheral blood mononuclear cells (PBMC) leads to upregulation of their NK cell cytotoxicity. The induction of NK cell activity by HHV-6 was abrogated by monoclonal antibodies (mAbs) to IL-15 but not by mAbs to other cytokines (IFN-alpha, IFN-gamma, TNF-alpha, TNF-beta, IL-2, IL-12) suggesting that IL-15 secreted in response to viral infection was responsible for the observed effect. Furthermore, NK activation by HHV-6 was blocked with mAb to CD122, as well as by human anti-HHV-6 neutralizing antibodies. Using RT-PCR, we were able to detect IL-15 mRNA upregulation in purified monocyte and NK cell preparations. IL-15 protein synthesis was increased in response to HHV-6. Finally, addition of IL-15 to PBMC cultures was found to severely curtail HHV-6 expression. Taken together, our data suggest that enhanced NK activity in response to viral infection represent a natural anti-viral defense mechanism aimed at rapidly eliminating virus-infected cells.
人类疱疹病毒6型（HHV-6）对自然杀伤（NK）细胞和T淋巴细胞具有显著的嗜性，这促使我们研究HHV-6对细胞毒性的影响。我们在此描述外周血单核细胞（PBMC）感染HHV-6如何导致其NK细胞毒性上调。HHV-6诱导的NK细胞活性被抗IL-15单克隆抗体（mAb）消除，但不被抗其他细胞因子（IFN-α、IFN-γ、TNF-α、TNF-β、IL-2、IL-12）的mAb消除，这表明病毒感染后分泌的IL-15是观察到的效应的原因。此外，HHV-6诱导的NK细胞活化被抗CD122 mAb以及人抗HHV-6中和抗体阻断。使用逆转录聚合酶链反应（RT-PCR），我们能够在纯化的单核细胞和NK细胞制剂中检测到IL-15 mRNA上调。IL-15蛋白合成因HHV-6而增加。最后，发现向PBMC培养物中添加IL-15会严重抑制HHV-6表达。综上所述，我们的数据表明，病毒感染后NK活性增强代表了一种旨在快速消除病毒感染细胞的天然抗病毒防御机制。
