INTERACTION OF HERPES-SIMPLEX VIRUS WITH MONONUCLEAR PHAGOCYTES IS DEPENDENT ON THE DIFFERENTIATION STAGE OF THE CELLS

The interaction of herpes simplex virus (HSV) with mononuclear phagocy tes (MP), i.e. monocytes and macrophages, is of importance for the pat hogenesis of HSV infections. MP are known to play a significant role i n the cellular defence against infections with HSV, but it has also be en shown that HSV-1 affects MP. The infection of these cells at differ ent stages of differentiation has different outcomes, and may result i n the alteration of important cellular functions. HSV-1 inhibits the m orphological differentiation of human monocytes, and this inhibition o ccurs 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 ma crophages on production of essential cytokines and related this effect to the reproduction of the virus. Blood-derived MP were cultured in v itro and inoculated with HSV at different stages of differentiation. R eplication of the virus was measured by infectivity titration, detecti on of HSV antigens by immunofluorescence and detection of HSV-specific mRNA. In monocytes, no viral replication and no production of late pr otein was seen. HSV IE gene was transcribed in monocytes from some don ors, but not from others. In macrophages, virus replicated, but less e fficiently than in fully permissive fibroblast cells. The production o f IL-1 beta, IL-6 and TNF-alpha in both non-permissive monocytes and p ermissive macrophages was assayed both at the transcriptional level, a s mRNA, and as protein released from the cells. Production of cytokine s 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 t he 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 d onors. Our results indicate a relation between permissiveness and cyto kine response in mononuclear phagocytes infected with HSV-1. Such a re lation may be of importance to both intrinsic and extrinsic defence me chanisms of MP against HSV-1. Our study also demonstrates that even th e functions of non-permissive cells such as blood-derived monocytes ma y be affected by viral infections.