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Interaction of herpes simplex virus with mononuclear phagocytes is dependent on the differentiation stage of the
T Bruun1, A K Kristoffersen, H Rollag
1Institute of Microbiology, University of Oslo, Rikshospitalet, Norway.
Abstract:
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.
Insights
Herpes simplex virus (HSV) impacts cytokine production in monocytes and macrophages, affecting cellular defense mechanisms. Even non-permissive monocytes show altered functions when infected by HSV-1, highlighting complex virus-cell interactions.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Mononuclear phagocytes (MP), including monocytes and macrophages, are crucial for cellular defense against herpes simplex virus (HSV) infections.
- HSV-1 infection can alter MP functions, with varying outcomes depending on the differentiation stage of these cells.
- HSV-1 inhibits the morphological differentiation of human monocytes, despite monocytes being non-permissive to HSV-1.
Purpose of the Study:
- To investigate the effect of HSV infection on cytokine production in monocytes and macrophages.
- To correlate HSV infection effects with viral replication in these cells.
- To understand the relationship between MP permissiveness to HSV-1 and their cytokine response.
Main Methods:
- Blood-derived MP were cultured in vitro and infected with HSV at different differentiation stages.
- Viral replication was assessed by infectivity titration, HSV antigen detection (immunofluorescence), and HSV-specific mRNA.
- Cytokine production (IL-1β, IL-6, TNF-α) was measured at both transcriptional (mRNA) and protein levels.
Main Results:
- No viral replication or late protein production was observed in monocytes; HSV IE gene transcription varied among donors.
- Macrophages supported viral replication, though less efficiently than fibroblasts.
- HSV-1 modulated cytokine production in both monocytes and macrophages, with discrepancies between mRNA and protein levels, suggesting translational regulation.
- Cytokine modulation differed between monocytes and macrophages and varied between donors.
Conclusions:
- A relationship exists between mononuclear phagocyte permissiveness to HSV-1 and their cytokine response.
- HSV-1 infection affects both permissive macrophages and non-permissive monocytes, impacting their functions and defense mechanisms.
- These findings are significant for understanding intrinsic and extrinsic MP defense against HSV-1 and the broader impact of viral infections on non-permissive cells.