SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells
نویسندگان
چکیده
منابع مشابه
SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcripti...
متن کاملSAMHD1 Restricts HIV-1 Replication and Regulates Interferon Production in Mouse Myeloid Cells
SAMHD1 restricts the replication of HIV-1 and other retroviruses in human myeloid and resting CD4(+) T cells and that is counteracted in SIV and HIV-2 by the Vpx accessory protein. The protein is a phosphohydrolase that lowers the concentration of deoxynucleoside triphosphates (dNTP), blocking reverse transcription of the viral RNA genome. Polymorphisms in the gene encoding SAMHD1 are associate...
متن کاملSAMHD1 protects cancer cells from various nucleoside-based antimetabolites
Recently, we demonstrated that sterile α motif and HD domain containing protein 1 (SAMHD1) is a major barrier in acute myelogenous leukemia (AML) cells to the cytotoxicity of cytarabine (ara-C), the most important drug in AML treatment. Ara-C is intracellularly converted by the canonical dNTP synthesis pathway to ara-CTP, which serves as a substrate but not an allosteric activator of SAMHD1. Us...
متن کاملSAMHD1 degradation enhances active suppression of dendritic cell maturation by HIV-1.
A hallmark of HIV-1 infection is the lack of sterilizing immunity. Dendritic cells (DCs) are crucial in the induction of immunity, and lack of DC activation might underlie the absence of an effective anti-HIV-1 response. We have investigated how HIV-1 infection affects maturation of DCs. Our data show that even though DCs are productively infected by HIV-1, infection does not induce DC maturati...
متن کاملCellular pharmacology of D-d4FC, a nucleoside analogue active against drug-resistant HIV.
The backbone of effective highly active antiretroviral therapy regimens for the treatment of HIV infections currently contains at least two nucleosides. Among the features that influence the potency of each component of a regimen and the overall efficacy of the combination are the cellular uptake and bioconversion of nucleoside analogues to their active triphosphate form, and the extent of poss...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Scientific Reports
سال: 2017
ISSN: 2045-2322
DOI: 10.1038/srep42824