1. SAMHD1 in Retroviral Restriction and Innate Immune Sensing--Should We Leash the Hound?
- Author
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Thomas Gramberg, Anna-Ursula Happel, and Alexandra Herrmann
- Subjects
0301 basic medicine ,Myeloid ,Anti-HIV Agents ,Autoimmunity ,HIV Infections ,Biology ,medicine.disease_cause ,Virus Replication ,Immunomodulation ,SAM Domain and HD Domain-Containing Protein 1 ,03 medical and health sciences ,Immune system ,Virology ,Drug Discovery ,medicine ,Animals ,Humans ,Viral Regulatory and Accessory Proteins ,Disease Resistance ,Monomeric GTP-Binding Proteins ,Innate immune system ,HIV ,vpr Gene Products, Human Immunodeficiency Virus ,Simian immunodeficiency virus ,Reverse transcriptase ,Immunity, Innate ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Viral replication ,Host-Pathogen Interactions ,Simian Immunodeficiency Virus ,SAMHD1 ,Protein Binding - Abstract
Background: The antiviral restriction factor SAM domain and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphohydrolase and thereby contributes to the regulation of intracellular dNTP levels. SAMHD1 blocks retroviral infection at the level of reverse transcription in myeloid cells and resting CD4+ T cells and is counteracted by the accessory protein Vpx, which is encoded by human immunodeficiency virus 2 (HIV-2) and several simian immunodeficiency virus (SIV) strains. Recently, it has been shown that the antiviral activity of SAMHD1 in myeloid dendritic cells (DC) hampers the induction of an efficient immune response directed against HIV-1. Conclusion: Within this review, we will summarize recent advances on the biology of SAMHD1 and its function as an antiviral restriction factor. In addition, we will discuss its role in autoimmunity and the antiviral immune response directed against HIV-1 and will evaluate the possibility of modulating SAMHD1 activity to generate an enhanced antiretroviral immune response.
- Published
- 2015