کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3421726 1226673 2015 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SAMHD1: At the Crossroads of Cell Proliferation, Immune Responses, and Virus Restriction
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروب شناسی
پیش نمایش صفحه اول مقاله
SAMHD1: At the Crossroads of Cell Proliferation, Immune Responses, and Virus Restriction
چکیده انگلیسی

SAMHD1 is a triphosphohydrolase enzyme that controls the intracellular level of deoxyribonucleoside triphosphates (dNTPs) and plays a role in innate immune sensing and autoimmune disease. SAMHD1 has also been identified as an intrinsic virus restriction factor, inactivated through degradation by HIV-2 Vpx or through a post-transcriptional regulatory mechanism. Phosphorylation of SAMHD1 by cyclin-dependent kinases has been strongly associated with inactivation of the virus restriction mechanism, providing an association between virus replication and cell proliferation. Tight regulation of cell proliferation suggests that viruses, particularly HIV-1 replication, latency, and reactivation, may be similarly controlled by multiple checkpoint mechanisms that, in turn, regulate dNTP levels. In this review, we discuss how SAMHD1 is a viral restriction factor, the mechanism associated with viral restriction, the pathway leading to its inactivation in proliferating cells, and how strategies aimed at controlling virus restriction could lead to a functional cure for HIV.

TrendsSAMHD1 is a host restriction factor that limits retroviral replication at the reverse transcription step, and it is counteracted by HIV-2 Vpx, which targets SAMHD1 for degradation by the proteasome.The mechanism of SAMHD1 virus restriction is controversial; both dNTPase and RNase functions have been proposed as essential for its antiviral activity. However, the exonuclease activity cannot be associated with the SAMHD1 active site.SAMHD1 restriction is deactivated by phosphorylation mediated by cyclin-dependent kinases and is tightly linked to cell-cycle entry and progression.Recent studies have established an association between SAMHD1 restriction, innate sensing of DNA, and protective immune responses.SAMHD1 links virus replication, innate immune responses, and cell-cycle progression, determining disease outcomes of viral infections, autoimmune diseases, and cancer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 23, Issue 11, November 2015, Pages 680–692
نویسندگان
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