ライフサイエンスコーパス: SAMHD1

1 ed host restriction factors (e.g., APOBEC3G, SamHD1).

2 HIV-1 infection in macrophages by regulating SAMHD1.

3 plasm, induce the proteasomal degradation of SAMHD1.

4 and N-terminal and SAM domains from mandrill SAMHD1.

5 s, and this effect is lost in the absence of SAMHD1.

6 ely suppressing DC maturation independent of SAMHD1.

7 d macrophages despite the restriction factor SAMHD1.

8 ecures CRL4 to degrade the antiviral protein SAMHD1.

9 AF1 and the carboxy-terminal region of human SAMHD1.

10 osphate and 5' carbon that potently inhibits SAMHD1.

11 both substrates and allosteric effectors for SAMHD1.

12 operties of pure recombinant human and mouse SAMHD1.

13 eoxynucleoside triphosphate phosphohydrolase SAMHD1.

14 nd increases the antiviral active isoform of SAMHD1.

15 ours the proteasome-dependent degradation of SAMHD1.

16 TM2 and suppressed expression of RNase L and SAMHD1.

17 x protein of HIV-2 and most SIVs counteracts SAMHD1.

18 roRNAs miR-181a, miR-30a, and miR-155 in the SAMHD1 3'-UTR.

19 de-like 3 (APOBEC3) cytidine deaminases, and SAMHD1 (a cell cycle-regulated dNTP triphosphohydrolase)

20 idine-aspartate domain-containing protein 1 (SAMHD1), a deoxyribonucleoside triphosphate triphosphohy

21 ha motif and HD domain-containing protein 1 (SAMHD1), a dNTPase, prevents the infection of nondividin

22 ated the influence of the restriction factor SAMHD1, a dNTP hydrolase (dNTPase) and RNase, on HBV rep

23 SAMHD1, a dNTP triphosphohydrolase, contributes to inter

24 The EC50(dNTP) values for SAMHD1 activation by dNTPs are in the 2-20 mum range, an

25 cells restrictive to retroviral replication, SAMHD1 activation is likely to be achieved through a dis

26 vealing the structural basis of GTP-mediated SAMHD1 activation.

27 on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease th

28 cers, that these mutations negatively affect SAMHD1 activity, and that several SAMHD1 mutations are f

29 etween control of the cell cycle by CDK6 and SAMHD1 activity, which is important for replication of l

30 Loss of SAMHD1 activity-through genetic depletion, mutational in

31 ions in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or MDA5.

32 In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form of Aicardi-Goutie

33 TREX1 (AGS1), RNase H2 (AGS2, 3 and 4), and SAMHD1 (AGS5).

34 se embryos revealed that inactivation of one SAMHD1 allele is sufficient to elevate dNTP pools.

35 An in vivo model is suggested where SAMHD1 alternates between the mutually exclusive functio

36 M domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV rep

37 The phenotypes associated with loss of samhd1 and adar suggest a function of these genes in con

38 We studied if SAMHD1 and dGK interact in the regulation of the dGTP po

39 Therefore, topoisomerase inhibitors regulate SAMHD1 and HIV permissivity at a post-RT step, revealing

40 t remains independent of restriction factors SAMHD1 and myxovirus resistance 2 (MX2).

41 persistent contaminants that co-purify with SAMHD1 and not from the HD active site.

42 ine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6,

43 biology of the restriction factors APOBEC3, SAMHD1 and tetherin and the viral accessory proteins tha

44 CRL4) by facilitating an interaction between SAMHD1 and the substrate receptor DDB1- and Cullin4-asso

45 Comparison of the wild-type SAMHD1 and the T592D mutant reveals that the phosphomime

46 cyclin A2, CDK2 phosphorylates T592 of human SAMHD1 and thereby regulates its HIV-1 restriction funct

47 ternative interaction interfaces are used by SAMHD1 and Vpx: the SAMHD1 N-terminal tail and the adjac

48 ctor genes, such as APOBEC3F/G, TRIM5-alpha, SAMHD1, and BST-2.

49 the 5'- and 3'-untranslated region (UTR) of SAMHD1, and the mechanism responsible for the cell type-

50 y, infection by HIV-2 and SIVsm encoding the SAMHD1 antagonist Vpx was insensitive to ETO treatment.

51 scular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid ti

52 Mutations in SAMHD1 are also implicated in the pathogenesis of chroni

53 spite the presence of the restriction factor SAMHD1, are unknown.

54 These results identify SAMHD1 as a potential biomarker for the stratification o

55 SAMHD1 can be regulated by dGTP, with which SAMHD1 assembles into catalytically active tetramers.

56 SAMHD1 associates with HIV-1 RNA and degrades it during

57 x/Vpr recognizes the host restriction factor SAMHD1 at either its N- or C-terminal tail and targets i

58 Furthermore, phosphorylation of SAMHD1 at T592 negatively regulates its RNase activity i

59 their effect on the phosphorylation of human SAMHD1 at T592.

60 in half-life, and optimal phosphorylation of SAMHD1 at Thr(592) Furthermore, we observed that SAMHD1

61 CyclinA2-CDK1/2 phosphorylates SAMHD1 at Thr-592, but how this modification controls SA

62 Phosphorylation of human SAMHD1 at threonine 592 (T592) by cyclin-dependent kinas

63 dies suggested that phosphorylation of human SAMHD1 at threonine 592 by CDK1 and cyclin A2 negatively

64 and CDK2, which mediates phosphorylation of SAMHD1 at threonine 592, a post-translational modificati

65 and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosp

66 nonical dNTP can bind to site 2 and activate SAMHD1, but in cells only dATP or dTTP are present at su

67 udy, we investigate allosteric activation of SAMHD1 by deoxynucleotide-dependent tetramerization and

68 ate details of clade-specific recognition of SAMHD1 by lentiviral Vpx proteins.

69 Down-regulation of SAMHD1 by siRNA expands all four dNTP pools, with dGTP u

70 We demonstrate that induction of SAMHD1 by type I and II interferons depends on 3'-UTR po

71 e bipartite cyclinA2-CDK-binding site in the SAMHD1 C terminus described herein abolished SAMHD1 phos

72 The dNTPase activity of SAMHD1 can be regulated by dGTP, with which SAMHD1 assem

73 ce of the long-lived activated state is that SAMHD1 can remain active long after dNTP pools have been

74 Here, we present the crystal structures of SAMHD1 catalytic core (residues 113-626) tetramers, comp

75 -length tetramerization and the structure of SAMHD1 catalytic core tetramer in complex with GTP/dATP,

76 e infection of T(SCM) cells, indicating that SAMHD1 contributes to abortive infection in these cells.

77 We conclude that the activity of SAMHD1 contributes to the pathological phenotype of dGK

78 MHD1 dNTPase in S phase, thereby fine-tuning SAMHD1 control of dNTP levels during DNA replication.

79 emonstrate that the interaction of CD81 with SAMHD1 controls the metabolic rate of HIV-1 replication

80 ects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing

81 Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with A

82 diamine (TPEN) potently blocked Vpx-mediated SAMHD1 degradation and inhibited wild-type SIVmac (simia

83 viral replication, Vpx has evolved to induce SAMHD1 degradation and Vpr to mediate HLTF degradation.

84 Fourth, SAMHD1 degradation by Vpx did not alter HIV-1 template s

85 dent on the presence of DCAF1 and results in SAMHD1 degradation in a proteasome- and DCAF1-dependent

86 , and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in S

87 d in the virion and is dedicated to inducing SAMHD1 degradation.

88 ted UNG2 degradation, and HIV-2 Vpx-mediated SAMHD1 degradation.

89 the CRL4 (DCAF1) E3 complex and Vpx-induced SAMHD1 degradation.

90 Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early

91 V-1 replication in vivo Finally, we reveal a SAMHD1-dependent antiretroviral activity of histone deac

92 SAMHD1-dependent dNTP depletion is thought to impair ret

93 ction at the reverse transcription step in a SAMHD1-dependent manner, reducing the intracellular dNTP

94 f p53, p21, decrease in CDK1 expression, and SAMHD1 dephosphorylation.

95 Notably, higher infection observed with SAMHD1 depletion correlated with a stronger suppression

96 ous disparate findings regarding the site of SAMHD1 depletion.

97 x relies on both CUL4A and CUL4B for maximal SAMHD1 depletion.

98 ore, our finding that intracellular CUL4 and SAMHD1 distributions can vary with cell type provides th

99 els, which is not consistent with a role for SAMHD1 dNTPase activity in HIV-1 restriction.

100 -592 phosphorylation state to the control of SAMHD1 dNTPase activity.

101 CDK down-modulates, but does not inactivate, SAMHD1 dNTPase in S phase, thereby fine-tuning SAMHD1 co

102 revented SAMHD1 phosphorylation and promoted SAMHD1 dNTPase-independent antiviral activity.

103 ed Langerhans cells (LC), but degradation of SAMHD1 does not rescue HIV-1 or vesicular stomatitis vir

104 th high variant allele frequency and reduced SAMHD1 expression and occur in 11% of relapsed/refractor

105 uggest the contribution of cyclin binding to SAMHD1 expression and stability in dividing cells.

106 SAMHD1 expression is differentially regulated by interfe

107 or latently infected at low levels, and that SAMHD1 expression promotes abortive infection of this im

108 aining therapy was inversely correlated with SAMHD1 expression.

109 via the accessory protein Vpx, which targets SAMHD1 for degradation through interactions with the hos

110 ich normally does not target wild type human SAMHD1 for degradation.

111 /HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellul

112 the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation.

113 iral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation.

114 sociated factor 1 (DCAF1), thereby targeting SAMHD1 for proteasome-dependent down-regulation.

115 imately 10 mum for mouse and 1 mum for human SAMHD1, for dTTP the corresponding values are 50 and 2 m

116 Cyclin L2 and SAMHD1 form a molecular complex that is partially depend

117 SAMHD1 forms tetramers that possess deoxyribonucleotide

118 The deoxyguanosine released by SAMHD1 from dGTP can be phosphorylated inside mitochondr

119 present biochemical analyses of GTP-induced SAMHD1 full-length tetramerization and the structure of

120 presented here advance our understanding of SAMHD1 function during cellular homeostasis.

121 SAMHD1 functions as an important retroviral restriction

122 Thr-592, but how this modification controls SAMHD1 functions in proliferating cells is not known.

123 expresses a green fluorescent protein (GFP)-SAMHD1 fusion protein, we showed that the Vpx-dependent

124 The host protein SAMHD1 has been identified as the first mammalian deoxyn

125 SAMHD1 has been reported to be able to degrade dNTPs and

126 M domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, low

127 Germ-line mutations in SAMHD1 have been described in patients with Aicardi-Gout

128 To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineage

129 Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic re

130 Sequence analysis of SAMHD1 identifies a putative cyclin-binding motif found

131 HIV-1 and HIV-2 with DNA repair enzymes and SAMHD1 imply that these viruses use different strategies

132 We obtained 26 crystal structures of SAMHD1 in complex with different combinations of GTP and

133 We demonstrated that silencing of SAMHD1 in hepatic cells increased HBV replication, while

134 Depletion of SAMHD1 in macrophages decouples the association between

135 block was completely rescued by depletion of SAMHD1 in MDM Concordantly, infection by HIV-2 and SIVsm

136 HIV-1 replication, the antiviral activity of SAMHD1 in our primary cell model appears to be, at least

137 ine derived from endogenous dGTP degraded by SAMHD1 in the nucleus.

138 Our results prove the importance of SAMHD1 in the regulation of all dNTP pools and suggest t

139 understanding of the important functions of SAMHD1 in the regulation of cellular dNTP levels, as wel

140 proteins that interact with human and mouse SAMHD1, including three previously unknown cellular prot

141 Consequently, CD81 depletion results in SAMHD1 increased expression, decreasing the availability

142 siRNA silencing of SAMHD1 increases dNTP pools, stops cycling human cells i

143 In conclusion, we report a SAMHD1-independent post-entry restriction in MDLC and LC

144 The lower Km constants for human SAMHD1 induce activation at lower cellular concentration

145 One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 in

146 Given the role of these SAMHD1-interacting proteins in cell cycle progression, w

147 activation regulate the expression of these SAMHD1-interacting proteins.

148 ibited Vpx and DCAF1 binding but not the Vpx-SAMHD1 interaction or Vpx virion packaging.

149 However, it is unclear whether human SAMHD1 interacts with other host proteins in the cyclin

150 We and others have reported that human SAMHD1 interacts with the cell cycle regulatory proteins

151 SAMHD1 is a cellular protein that plays key roles in HIV

152 SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosp

153 SAMHD1 is a deoxynucleoside triphosphate triphosphohydro

154 SAMHD1 is a dNTP hydrolase, whose activity is required f

155 SAMHD1 is a GTP-activated nonspecific dNTP triphosphohyd

156 ynucleoside triphosphate triphosphohydrolase SAMHD1 is a myeloid cell-specific retroviral restriction

157 These results suggest that SAMHD1 is a non-classical interferon-stimulated gene reg

158 The dNTP triphosphohydrolase SAMHD1 is a nuclear antiviral host restriction factor li

159 SAMHD1 is a nuclear deoxyribonucleoside triphosphate tri

160 SAMHD1 is a phosphohydrolase maintaining cellular dNTP h

161 These results suggest that SAMHD1 is a relevant restriction factor for HBV and rest

162 The HIV-1 restriction factor SAMHD1 is a tetrameric enzyme activated by guanine nucle

163 lization approaches, we show that endogenous SAMHD1 is able to interact with the cyclin A-CDK1-CDK2 c

164 Our data demonstrate how SAMHD1 is activated by binding of GTP or dGTP at alloste

165 Here, we establish that SAMHD1 is activated by GTP binding to guanine-specific a

166 Tetrameric SAMHD1 is activated for the hydrolysis of any dNTP only

167 Here we show that SAMHD1 is also expressed in epidermis-isolated Langerhan

168 f this CD4(+) T cell subset, indicating that SAMHD1 is an active restriction factor in T(SCM) cells.

169 SAMHD1 is an intracellular enzyme that specifically degr

170 In cultured human fibroblasts SAMHD1 is expressed maximally during quiescence preventi

171 FP.SAM595 in which the Vpx binding domain of SAMHD1 is fused to the carboxy terminus of green fluores

172 Although the physiological function of SAMHD1 is largely unknown, this review provides perspect

173 We propose that in quiescent cells where SAMHD1 is maximally expressed GTP binds to site 1 with v

174 The anti-HIV-1 activity of SAMHD1 is negatively modulated by phosphorylation at res

175 Thus, cellular regulation of active SAMHD1 is not determined by GTP alone but instead, the l

176 findings help define the mechanisms by which SAMHD1 is phosphorylated and suggest the contribution of

177 The restriction ability of SAMHD1 is regulated in cells by phosphorylation on T592.

178 ur results reveal that the RNase activity of SAMHD1 is responsible for preventing HIV-1 infection by

179 nd we hypothesize that enzymatic activity of SAMHD1 is subject to additional cellular regulatory mech

180 ontroversial whether the dNTPase activity of SAMHD1 is sufficient for restriction.

181 as localized to the nucleus, confirming that SAMHD1 is targeted in the nucleus and thus explaining wh

182 to Vpx-mediated degradation, confirming that SAMHD1 is targeted in the nucleus.

183 SAMHD1 is the first dNTP triphosphohydrolase found in ma

184 ha motif and HD domain-containing protein-1 (SAMHD1) is a recently described deoxynucleotide phosphoh

185 idine-aspartate domain-containing protein 1 (SAMHD1) is a tetrameric protein that catalyzes the hydro

186 domain- and HD domain-containing protein 1 (SAMHD1) is proposed to inhibit HIV-1 replication by depl

187 Therefore, cyclin L2-mediated control of SAMHD1 levels in macrophages supports HIV-1 replication.

188 Here, we show that SAMHD1 levels remain relatively unchanged during the cel

189 The restriction factor SAMHD1 limits HIV-1 replication in noncycling cells.

190 We propose that SAMHD1 may have a function in DNA repair and that the pr

191 ncing of the TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes.

192 dNTP depletion is not the sole mechanism of SAMHD1-mediated HIV-1 restriction.

193 SAMHD1-mediated retroviral restriction is thought to res

194 ch is summarized and the mechanisms by which SAMHD1 mediates retroviral restriction are analyzed.

195 D1 at Thr(592) Furthermore, we observed that SAMHD1 mutants of the cyclin-binding motif mislocalized

196 exerted by Thr-592 phosphorylation-defective SAMHD1 mutants were associated with activation of DNA da

197 ic lymphocytic leukemia (CLL), we revealed a SAMHD1 mutation as a potential founding event.

198 AGS patient carrying a pathogenic germ-line SAMHD1 mutation who developed CLL at 24 years of age.

199 linical trial samples, we show that acquired SAMHD1 mutations are associated with high variant allele

200 ely affect SAMHD1 activity, and that several SAMHD1 mutations are found in tumors with defective mism

201 ction in DNA repair and that the presence of SAMHD1 mutations in CLL promotes leukemia development.

202 suggest that heterozygous cancer-associated SAMHD1 mutations increase mutation rates in cancer cells

203 SAMHD1 mutations that interfere with the dNTPase activit

204 s of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ub

205 details of Vpx lineage-specific targeting of SAMHD1 N-terminal "degron" sequences.

206 n interfaces are used by SAMHD1 and Vpx: the SAMHD1 N-terminal tail and the adjacent SAM domain or th

207 et al. (2015) report the structural basis of SAMHD1 N-terminal targeting by Vpx.

208 itional host proteins interacting with human SAMHD1, namely, cyclin-dependent kinase 2 (CDK2) and S-p

209 s are observed in immune cells cultured from Samhd1 null mouse models, these mice are physically heal

210 in human SAMHD1 to Phe, the residue found in SAMHD1 of Red-capped monkey and Mandrill, allows it to b

211 e degradation of the host restriction factor SAMHD1 or host helicase transcription factor (HLTF), res

212 Furthermore, loss of samhd1 or of another AGS-associated gene, adar, leads to

213 in a virion also needs to clear the cell of SAMHD1 over a prolonged period of time.

214 se results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction

215 er mutation of the catalytic residues of the SAMHD1 phosphohydrolase domain or by a Thr-592 phosphomi

216 ed to cell cycle progression and coordinated SAMHD1 phosphorylation and inactivation.

217 In parallel, p21 prevented SAMHD1 phosphorylation and promoted SAMHD1 dNTPase-indep

218 s provide a mechanistic understanding of how SAMHD1 phosphorylation at residue Thr-592 may modulate i

219 as an upstream regulator of CDK2 controlling SAMHD1 phosphorylation in primary T cells and macrophage

220 SAMHD1 C terminus described herein abolished SAMHD1 phosphorylation on Thr-592 during S and G2 phases

221 radation, dNTP pool elevation, or changes in SAMHD1 phosphorylation.

222 idine-aspartate domain-containing protein 1 (SAMHD1) plays a critical role in inhibiting HIV infectio

223 Here, we show that SAMHD1 possesses RNase activity and that the RNase but n

224 SAMHD1 potently blocks HIV-1 replication in DCs, althoug

225 the trace exonuclease activities detected in SAMHD1 preparations arise from persistent contaminants t

226 for the cell type-dependent up-regulation of SAMHD1 protein by interferon.

227 es perspectives about the role of endogenous SAMHD1 protein in maintaining normal cellular function,

228 SAMHD1 protein is highly expressed in human myeloid-line

229 and miR-30a levels inversely correlates with SAMHD1 protein up-regulation upon type I and II interfer

230 than those seen upon expression of wild type SAMHD1 protein.

231 tidine aspartic domain containing protein 1 (SAMHD1) protein, when compared with activated CD4(+) T c

232 Human and mouse SAMHD1 proteins block HIV-1 infection in noncycling cell

233 In the presence of SAMHD1 quiescent mutant fibroblasts manifested mt dNTP p

234 letion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells.

235 We provide evidence that SAMHD1 regulates cell proliferation and survival and eng

236 However, phosphorylation of SAMHD1 regulates its ability to restrict HIV-1 without d

237 Here, we report that SAMHD1 regulation of the dNTP concentrations influences

238 In particular, SAMHD1-related AGS is associated with a distinctive cere

239 or generating a clinically relevant model of SAMHD1-related AGS.

240 ic cells, and consequently protein levels of SAMHD1 remain unchanged.

241 In this review, the latest progress on SAMHD1 research is summarized and the mechanisms by whic

242 ation that has been implicated in abrogating SAMHD1 restriction function and ability to form stable t

243 Interfering with SAMHD1 restriction further increased infection of DCs, b

244 ated simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral ac

245 The deoxyribonucleotide triphosphohydrolase SAMHD1 restricts lentiviral infection by depleting the d

246 SAMHD1 restricts lentiviral replication in myeloid cells

247 f domain and HD domain-containing protein 1 (SAMHD1) restricts human immunodeficiency virus type 1 (H

248 stidine/aspartate (HD)-containing protein 1 (SAMHD1) restricts human/simian immunodeficiency virus in

249 The depletion of the restriction factor SAMHD1 resulted in a markedly increased number of EdU pu

250 we report that AGS gene silencing of TREX1, SAMHD1, RNASEH2A, and ADAR1 by short hairpin RNAs in hum

251 Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog deri

252 s directing Vpx lineages to N- or C-terminal SAMHD1 sequences.

253 cyclin A2 and CDK1 complex and whether mouse SAMHD1 shares similar cellular interacting partners.

254 Third, differentiated SAMHD1 shRNA THP-1 cells have a 2-fold increase in HIV-1

255 SAMHD1 significantly affected the levels of extracellula

256 by HIV, and we demonstrate that knockdown of SAMHD1 significantly increases the frequency of infectio

257 SAMHD1 silencing in macrophages and CD4(+) T cells from

258 We observed that mouse SAMHD1 specifically interacted with cyclin A2, cyclin B1

259 SAMHD1 (sterile alpha motif and HD domain-containing pro

260 SAMHD1 (sterile alpha motif and histidine (H) aspartate

261 ng mutants of human HIV-1 restriction factor SAMHD1 suggests that it inhibits infection through degra

262 SAMHD1 suppresses viral reverse transcription (RT) throu

263 ting in upregulation of CDK1 with subsequent SAMHD1 T592 phosphorylation and deactivation of its anti

264 mutation T592E reduces the stability of the SAMHD1 tetramer and the dNTPase activity of the enzyme.

265 ults reveal an ordered model for assembly of SAMHD1 tetramer from its inactive monomer and dimer form

266 t allosteric and four catalytic sites of the SAMHD1 tetramer.

267 te the impact of phosphomimetic mutations on SAMHD1 tetramerization and dNTPase activity in vitro.

268 t that the effect of T592 phosphorylation on SAMHD1 tetramerization is not likely to explain the retr

269 ificant decrease in the population of active SAMHD1 tetramers, and hence the dNTPase activity is subs

270 macrophages express a phosphorylated form of SAMHD1 that corresponds with susceptibility to infection

271 rolase-independent, moonlighting function of SAMHD1 that facilitates homologous recombination of DNA

272 s results in a long-lived tetrameric form of SAMHD1 that persists for hours, even after activating nu

273 le of these cellular interacting partners of SAMHD1 that regulate its HIV-1 restriction function.

274 y affect protein level or phosphorylation of SAMHD1, the virus upregulated intracellular dATPs.

275 screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retro

276 how that changing the single Ser-52 in human SAMHD1 to Phe, the residue found in SAMHD1 of Red-capped

277 We cannot rule out a contribution of SAMHD1 to retroviral restriction in relatively non-permi

278 The contributions of SAMHD1 to retroviral restriction in the central nervous

279 Current evidence indicates that Vpx recruits SAMHD1 to the Cullin4-Ring Finger E3 ubiquitin ligase (C

280 Accordingly, we investigated SAMHD1 transcript abundance and association with the Typ

281 SAMHD1 transcript levels were IFN responsive, increasing

282 In vitro, SAMHD1 transcript was abundant in macaque astrocytes and

283 Both Type I and II interferons may stimulate SAMHD1 transcription.

284 The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of m

285 Knockdown of the HIV restriction factor SAMHD1 using Vpx-containing simian immunodeficiency viru

286 sms, we determined the crystal structures of SAMHD1 variants T592E and T592V.

287 This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substra

288 We report that SAMHD1 was activated by dephosphorylation following ETO

289 Interestingly, SAMHD1 was dephosphorylated, thus in a potentially antiv

290 Monomeric SAMHD1 was found to bind preferentially to single-strand

291 Elevated SAMHD1 was localized to endothelial cells, perivascular

292 SAMHD1 was purified using three chromatography steps, ov

293 Moreover, HBV restriction by SAMHD1 was rescued by addition of deoxynucleosides.

294 When SAMHD1 was silenced by siRNA transfection the compositio

295 Furthermore, SAMHD1 was upregulated by type I and II interferons in h

296 d histidine-aspartic (HD) domains protein 1 (SAMHD1) was previously identified as a critical post-ent

297 Using temporal gene knockdown of zebrafish samhd1, we observe hindbrain ventricular swelling and br

298 SAM-domain and HD-domain containing protein (SAMHD1), which depletes free nucleotides, blocking rever

299 tic and nucleotide activator site mutants of SAMHD1 with no dNTPase activity retained the exonuclease

300 We hypothesized that SAMHD1 would respond to interferon in the SIV-infected C