Herrmann Alexandra, Happel Anna-Ursula, Gramberg Thomas
Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.
Curr HIV Res. 2016;14(3):225-34. doi: 10.2174/1570162x14999160224102515.
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.
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.
抗病毒限制因子含SAM结构域和HD结构域蛋白1（SAMHD1）是一种脱氧核苷三磷酸三磷酸水解酶，因此有助于调节细胞内脱氧核苷三磷酸水平。SAMHD1在髓样细胞和静息CD4+T细胞的逆转录水平上阻断逆转录病毒感染，并被辅助蛋白Vpx所抵消，Vpx由人类免疫缺陷病毒2（HIV-2）和几种猴免疫缺陷病毒（SIV）毒株编码。最近的研究表明，SAMHD1在髓样树突状细胞（DC）中的抗病毒活性会阻碍针对HIV-1的有效免疫反应的诱导。
在本综述中，我们将总结SAMHD1生物学及其作为抗病毒限制因子功能的最新进展。此外，我们将讨论其在自身免疫以及针对HIV-1的抗病毒免疫反应中的作用，并评估调节SAMHD1活性以产生增强的抗逆转录病毒免疫反应的可能性。
