Bruun T, Kristoffersen A K, Rollag H, Degré M
Institute of Microbiology, University of Oslo, Rikshospitalet, Norway.
APMIS. 1998 Feb;106(2):305-14. doi: 10.1111/j.1699-0463.1998.tb01351.x.
The interaction of herpes simplex virus (HSV) with mononuclear phagocytes (MP), i.e. monocytes and macrophages, is of importance for the pathogenesis of HSV infections. MP are known to play a significant role in the cellular defence against infections with HSV, but it has also been shown that HSV-1 affects MP. The infection of these cells at different stages of differentiation has different outcomes, and may result in the alteration of important cellular functions. HSV-1 inhibits the morphological differentiation of human monocytes, and this inhibition occurs in spite of the fact that human monocytes are non-permissive to HSV-1. We have studied the effect of HSV infection of monocytes and macrophages on production of essential cytokines and related this effect to the reproduction of the virus. Blood-derived MP were cultured in vitro and inoculated with HSV at different stages of differentiation. Replication of the virus was measured by infectivity titration, detection of HSV antigens by immunofluorescence and detection of HSV-specific mRNA. In monocytes, no viral replication and no production of late protein was seen. HSV IE gene was transcribed in monocytes from some donors, but not from others. In macrophages, virus replicated, but less efficiently than in fully permissive fibroblast cells. The production of IL-1 beta, IL-6 and TNF-alpha in both non-permissive monocytes and permissive macrophages was assayed both at the transcriptional level, as mRNA, and as protein released from the cells. Production of cytokines by MP was affected by HSV-1. The level of cytokine mRNA and cytokine protein did not correspond for all cytokines, which may suggest that translational regulation and/or cytokine inhibitors are important in the regulation of the cytokine response. The cytokine modulation, both at the transcriptional level and measured as biological activity, was different in monocytes and macrophages, and varied between different donors. Our results indicate a relation between permissiveness and cytokine response in mononuclear phagocytes infected with HSV-1. Such a relation may be of importance to both intrinsic and extrinsic defence mechanisms of MP against HSV-1. Our study also demonstrates that even the functions of non-permissive cells such as blood-derived monocytes may be affected by viral infections.
单纯疱疹病毒（HSV）与单核吞噬细胞（MP），即单核细胞和巨噬细胞的相互作用，对于HSV感染的发病机制至关重要。已知MP在针对HSV感染的细胞防御中发挥重要作用，但也已表明HSV-1会影响MP。在这些细胞分化的不同阶段进行感染会产生不同的结果，并可能导致重要细胞功能的改变。HSV-1抑制人类单核细胞的形态分化，尽管人类单核细胞对HSV-1不敏感，但这种抑制仍会发生。我们研究了HSV感染单核细胞和巨噬细胞对必需细胞因子产生的影响，并将这种影响与病毒的复制联系起来。将源自血液的MP在体外培养，并在分化的不同阶段接种HSV。通过感染性滴定、免疫荧光检测HSV抗原以及检测HSV特异性mRNA来测量病毒的复制。在单核细胞中，未观察到病毒复制和晚期蛋白的产生。来自一些供体的单核细胞中HSV IE基因被转录，但其他供体的则未转录。在巨噬细胞中，病毒能够复制，但效率低于完全敏感的成纤维细胞。在非敏感的单核细胞和敏感的巨噬细胞中，均在转录水平（作为mRNA）以及从细胞中释放的蛋白质水平上检测了IL-1β、IL-6和TNF-α的产生。MP产生细胞因子受到HSV-1的影响。并非所有细胞因子的细胞因子mRNA水平和细胞因子蛋白水平都相符，这可能表明翻译调控和/或细胞因子抑制剂在细胞因子反应的调节中很重要。在转录水平以及作为生物活性测量时，细胞因子调节在单核细胞和巨噬细胞中有所不同，并且在不同供体之间也存在差异。我们的结果表明，感染HSV-1的单核吞噬细胞的敏感性与细胞因子反应之间存在关联。这种关联可能对MP针对HSV-1的内在和外在防御机制都很重要。我们的研究还表明，即使是像源自血液的单核细胞这样的非敏感细胞的功能也可能受到病毒感染的影响。
