2017
DOI: 10.1002/rmv.1931
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Roles of SAMHD1 in antiviral defense, autoimmunity and cancer

Abstract: The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1 (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. This antiviral enzymatic activity can be inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx cau… Show more

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Cited by 28 publications
(20 citation statements)
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References 134 publications
(341 reference statements)
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“…Mice lacking ERAP1 had reduced numbers of both Tr1-like regulatory T cells and tolerogenic dendritic cells (54), suggesting that increased ERAD1 expression could be associated with increased numbers of these tolerogenic cell types in the spleen in response to kynurenine administration. SAM and HD domain-containing protein 1 (SAMHD1) is involved in anti-viral responses (55). Two ribonucleoproteins that have been associated with apoptosis were downregulated at 8 h, including heterogeneous nuclear ribonucleoproteins A2/B1 (reduced ratios of −1.17 and −1.15 in two spots) and heterogeneous nuclear ribonucleoprotein K (hnRNPK: reduced ratio of −1.36).…”
Section: Mass Spectroscopy; Acute (8 H) Groupmentioning
confidence: 99%
“…Mice lacking ERAP1 had reduced numbers of both Tr1-like regulatory T cells and tolerogenic dendritic cells (54), suggesting that increased ERAD1 expression could be associated with increased numbers of these tolerogenic cell types in the spleen in response to kynurenine administration. SAM and HD domain-containing protein 1 (SAMHD1) is involved in anti-viral responses (55). Two ribonucleoproteins that have been associated with apoptosis were downregulated at 8 h, including heterogeneous nuclear ribonucleoproteins A2/B1 (reduced ratios of −1.17 and −1.15 in two spots) and heterogeneous nuclear ribonucleoprotein K (hnRNPK: reduced ratio of −1.36).…”
Section: Mass Spectroscopy; Acute (8 H) Groupmentioning
confidence: 99%
“…Compared to the rest of the population, GEMM cells contained higher levels (median ratio, ∼ 1.5-fold) of transcripts encoding sensors of viral double-stranded DNA and RNA, such as IFI16 [66], HMGB1 [67], DDX58/RIG-I [68], IFIH1/MDA5 [69] and EIF2AK2/PKR [70], of signaling mediators like STAT1, and of transcriptional activators such as IRF3, IRF7 and IRF8 [71], but lower levels (median ratio, ∼ 4-fold) of negative regulators of IFN production and signaling such as IRF2 [72], IRF4 [73], TRAFD1 [74] and SOCS1 [75]. Expression of IFN effectors including IFIT1, IFIT2 and IFIT3, which recognize and prevent translation of virally produced triphosphorylated RNA molecules [76], IFITM1, IFITM2 and IFITM3, which block infection at multiple steps including entry [77], ISG15 and its conjugating (HERC5) and de-conjugating (USP18) enzymes, which disrupt the activity of viral proteins by ISGylation [78], as well as of known (MX1, MX2, OAS1, OAS2, OAS3 and OASL) [79, 80], or suspected anti-viral proteins such as viperin [81], SAMHD1 [82] and ISG20 [83] were instead similarly abundant in GEMM and the rest of the cells (median ratio, ∼ 1.1-fold) (Fig 10, GEMM/REST column).…”
Section: Resultsmentioning
confidence: 99%
“…Additionally, SAMHD1 expression may be differentiation dependent: SAMHD1 protein expression is greatly increased in PMA-treated THP-1 cells displaying a nondividing phenotype when compared to untreated dividing populations [12,42,44]. Type I interferon stimulation has been seen to induce SAMHD1 expression in primary monocytes [61,62], microglia [63], astrocytes [63,64], liver cells [50,65], HEK293T, and HeLa [66,67] cells while having no effect on protein expression in CD4+ cells [66], dendritic cells [66], MDDCs [12,66], and MDMs [12,68], information that is well summarized in a 2017 review by Jun Li's group [69]. It is important to note that SAMHD1 expression levels do not necessarily correlate with its dNTPase activity and cellular dNTP pools.…”
Section: Samhd1 Protein Contains An Nls and Is Expressed In A Varietymentioning
confidence: 99%