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The use of microRNA by human viruses: lessons from NK cells and HCMV infection

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Abstract

Depending on ethnicity and on social conditions, between 40 and 90 % of the population is infected with human cytomegalovirus (HCMV). In immunocompetent patients, the virus may cause an acute disease and then revert to a state of latency, which enables its coexistence with the human host. However, in cases of immunosuppression or in neonatal infections, HCMV can cause serious long-lasting illnesses. HCMV has developed multiple mechanisms in order to escape its elimination by the immune system, specifically by two killer cell types of the adaptive and the innate immune systems; cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, respectively. Another fascinating aspect of HCMV is that like other highly developed herpesviruses, it expresses its own unique set of microRNAs. Here, we initially describe how the activity of NK cells is regulated under normal conditions and during infection. Then, we discuss what is currently known about HCMV microRNA-mediated interactions, with special emphasis on immune modulation and NK cell evasion. We further illustrate the significant modulation of cellular microRNAs during HCMV infection. Although, the full target spectrum of HCMV microRNAs is far from being completely elucidated, it can already be concluded that HCMV uses its “multitasking” microRNAs to globally affect its own life cycle, as well as important cellular and immune-related pathways.

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Acknowledgments

This study was supported by funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement number 320473-BacNK. Further support came from the GIF foundation, from the Lewis family foundation, the ICRF professorship grant, the Israeli Science Foundation, the Helmhotz Association, and the Rosetrees Trust (all to O.M.). O.M. is a Crown Professor of Molecular Immunology.

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  1. The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem, 91120, Israel

    Tal Goldberger & Ofer Mandelboim

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  1. Tal Goldberger
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Correspondence to Ofer Mandelboim.

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This article is a contribution to the special issue on Immune Modulation, properties and models of CMV - Guest Editor: Ofer Mandelboim

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Goldberger, T., Mandelboim, O. The use of microRNA by human viruses: lessons from NK cells and HCMV infection. Semin Immunopathol 36, 659–674 (2014). https://doi.org/10.1007/s00281-014-0447-3

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