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Intertwined: SAMHD1 cellular functions, restriction, and viral evasion strategies

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Abstract

SAMHD1 was initially described for its ability to efficiently restrict HIV-1 replication in myeloid cells and resting CD4+ T cells. However, a growing body of evidence suggests that SAMHD1-mediated restriction is by far not limited to lentiviruses, but seems to be a general concept that applies to most retroviruses and at least a number of DNA viruses. SAMHD1 anti-viral activity was long believed to be solely due to its ability to deplete cellular dNTPs by enzymatic degradation. However, since its discovery, several new functions have been attributed to SAMHD1. It has been demonstrated to bind nucleic acids, to modulate innate immunity, as well as to participate in the DNA damage response and resolution of stalled replication forks. Consequently, it is likely that SAMHD1-mediated anti-viral activity is not or not exclusively mediated through its dNTPase activity. Therefore, in this review, we summarize current knowledge on SAMHD1 cellular functions and systematically discuss how these functions could contribute to the restriction of a broad range of viruses besides retroviruses: herpesviruses, poxviruses and hepatitis B virus. Furthermore, we aim to highlight different ways how viruses counteract SAMHD1-mediated restriction to bypass the SAMHD1-mediated block to viral infection.

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Acknowledgements

We would like to thank Kerstin Schott and Lise Lauterbach-Rivière for critical comments on the manuscript. This study was supported by the Deutsche Forschungsgemeinschaft (DFG; CRC1292 Project TP04 to R.K. and SPP1923 Project KO 4573/1-1 to R.K.) and by Deutsches Zentrum für Infektionsforschung (HZI2016Z10).

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  1. Renate König

    Present address: Host-Pathogen Interactions, Paul-Ehrlich-Institute, 63225, Langen, Germany

  2. Catharina Majer and Moritz Schüssler contributed equally to this work.

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  1. Host-Pathogen Interactions, Paul-Ehrlich-Institute, 63225, Langen, Germany

    Catharina Majer, Jan Moritz Schüssler & Renate König

  2. Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA

    Renate König

  3. German Center for Infection Research (DZIF), 63225, Langen, Germany

    Renate König

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Majer, C., Schüssler, J.M. & König, R. Intertwined: SAMHD1 cellular functions, restriction, and viral evasion strategies. Med Microbiol Immunol 208, 513–529 (2019). https://doi.org/10.1007/s00430-019-00593-x

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  • DOI: https://doi.org/10.1007/s00430-019-00593-x

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