ライフサイエンスコーパス: tetherin

1 he activity of Vpu to down-regulate cellular tetherin.

2 by counteracting the host restriction factor tetherin.

3 olates can acquire the ability to counteract tetherin.

4 ates with significant activity against human tetherin.

5 tetherin to neutralize the antiviral factor tetherin.

6 HIV-1 group M isolates use Vpu to counteract tetherin.

7 on factors, including APOBEC3F, APOBEC3G and tetherin.

8 enhancing HIV infection by counteraction of Tetherin.

9 ss from hepatocytes through the induction of tetherin.

10 ble of antagonizing ancestral Cercopithecini tetherin.

11 C as a function of its ability to counteract tetherin.

12 structure of SIV Nef complexed with AP-2 and tetherin.

13 ticle without downregulating plasma membrane tetherin.

14 n U (Vpu), which down-regulates and degrades tetherin.

15 in to antagonize the host restriction factor tetherin.

16 mice encoding endocytosis-defective NZW/LacJ Tetherin.

17 at SIVcpz Nef protein antagonizes chimpanzee tetherin.

18 bona fide antagonist of red-capped mangabey tetherin.

19 nism of virus-induced signal transduction by tetherin.

20 assay, and to determine sensitivity to human tetherin.

21 does not act by downregulating or degrading tetherin.

22 lize the viral protein U (Vpu) to counteract tetherin.

23 intrinsic host restriction factors, such as tetherin.

24 restriction by human tetherin but not mouse tetherin.

25 group O viruses is also active against human tetherin.

26 ction have used different assays for CD4 and tetherin.

27 surface retention by the restriction factor tetherin.

28 erpes simplex virus 1 (HSV-1) is targeted by tetherin.

29 ce expression of the host restriction factor tetherin.

30 ptake of an endocytosis-deficient variant of tetherin.

31 r blocking NF-kappaB signaling downstream of tetherin.

32 act the restriction factor and innate sensor tetherin.

33 ein evolved an effective antagonism of human tetherin.

34 the human ortholog of the restriction factor tetherin.

35 ng both the long and short isoforms of human tetherin.

36 roteins to counteract the restriction factor tetherin.

37 to distal cells were dramatically reduced by tetherin.

38 lved Vpu as an effective antagonist of human tetherin.

39 ur observations led to the identification of tetherin.

40 roup M uses Vpu instead of Nef to counteract tetherin.

41 duction of HBV virion release, we found that tetherin, a broad-spectrum antiviral transmembrane prote

42 presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic

43 nking regulator filamin A (FLNa) in Vpu anti-tetherin activities.

44 While both RBF206 Vpu and Nef exert anti-tetherin activity in transient-transfection assays, main

45 HIV-1 group O, which lacks Vpu-mediated anti-tetherin activity, acquired a Nef protein that is able t

46 ere critical for the acquisition of its anti-tetherin activity, RBF206 O-Vpu potently suppresses NF-k

47 eins from several of these viruses lack anti-tetherin activity, suggesting that under certain circums

48 glycoprotein M (gM) as having moderate anti-tetherin activity.

49 rotein bone marrow stromal antigen-2 (BST-2)/tetherin acts against a variety of enveloped viruses by

50 The results demonstrate that Tetherin acts as a modulator of the cell-mediated immune

51 ble tetherin transgene in order to study how tetherin affects retroviral dissemination and on which c

52 HIV Vpu-mediated degradation of tetherin allows efficient particle release and hampers t

53 Tetherin, also known as bone marrow stromal antigen 2 (B

54 BST2/tetherin, an antiviral restriction factor, inhibits the

55 ltaneously investigate Vpu-targeting of both tetherin and a viral glycoprotein, gibbon ape leukemia v

56 Alpha interferon (IFN-alpha) induced tetherin and blocked feline immunodeficiency virus (FIV)

57 Downregulation of BST-2/tetherin and CD4 by HIV-1 viral protein U (Vpu) promotes

58 To elucidate the roles of tetherin and cell-free virions during in vivo viral diss

59 ticity of HIV-1 in overcoming restriction by tetherin and challenge the prevailing view that all HIV-

60 e ancestral sequence of tribe Cercopithecini tetherin and demonstrate that all Nef proteins are capab

61 We also found colocalization of tetherin and HBV L protein at the intracellular multives

62 ion dissemination via plasma is inhibited by tetherin and is required for full MoMLV pathogenesis.IMP

63 including significantly higher induction of tetherin and MX2, increased APOBEC3G signature mutations

64 reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cry

65 oup O Vpu that efficiently antagonizes human tetherin and suggest that counteraction by O-Nefs may be

66 We demonstrate that FLNa associates with tetherin and that FLNa modulates tetherin turnover.

67 the restriction factors APOBEC3, SAMHD1 and tetherin and the viral accessory proteins that counterac

68 n down-regulating cell-surface expression of tetherin and thereby contributes to HIV-1 assembly and r

69 1 group M exclusively uses Vpu to counteract tetherin and underscore the importance of tetherin antag

70 onary interplay between tribe Cercopithecini tetherin and viral antagonists, Nef and Vpu.

71 f VP40 to restriction by human but not mouse tetherin and with changes in VP40 oligomerization.

72 f-NL4-3 are similarly restricted by PTM BST2/Tetherin, and neither virus downregulates it from the su

73 ow that HIV-1 group O uses Nef to antagonize tetherin, and that this activity may have contributed to

74 tween intrinsic anti-viral proteins, such as tetherin, and viral antagonists.

75 ct tetherin and underscore the importance of tetherin antagonism for efficient viral replication.

76 of tetherin's antiviral activities and viral tetherin antagonism have been studied in detail for a nu

77 We report that mutations in Vpu that impair tetherin antagonism increase the susceptibility of HIV-i

78 ly in humans, it has not evolved a Vpu-based tetherin antagonism.

79 It turns out that the FIV tetherin antagonist is also its Env protein, but the mec

80 demic HIV-1 group M strains evolved Vpu as a tetherin antagonist, while the Nef protein of less wides

81 Unlike other tetherin antagonists, FIV Env cannot act in trans to res

82 In response, many viruses have evolved tetherin antagonists.

83 CD4 and BST-2/Tetherin are cellular membrane proteins targeted to degr

84 ity, we describe possible scenarios by which tetherin arose that exemplify how protein modularity, ev

85 ovirus adaptation to new hosts and implicate tetherin as a filovirus host restriction factor.

86 These studies implicate Vpu antagonism of tetherin as an ADCC evasion mechanism that prevents anti

87 e transmembrane domain in the restriction of tetherin, as previously reported, but not of GaLV Env.

88 Tetherin-associated DC activation during acute FV infect

89 herin or overexpression of dominant negative tetherin attenuated the IFN-alpha-mediated reduction of

90 The tetherin binding site in Nef is distinct from those of m

91 us macaques results in rapid upregulation of tetherin (BST-2 or CD317) on peripheral blood lymphocyte

92 heir Vpu proteins to overcome restriction by tetherin (BST-2 or CD317), which is a transmembrane prot

93 The interferon-inducible membrane protein tetherin (Bst-2, or CD317) is an antiviral factor that i

94 Tetherin/BST-2 (here called tetherin) is an antiviral pr

95 Tetherin/BST-2 is a host restriction factor that could d

96 Tetherin/BST-2 is a host restriction factor that inhibit

97 Tetherin/BST-2 is a restriction factor, originally descr

98 Tetherin/BST-2 is an antiviral protein that blocks the r

99 Tetherin (BST2, CD317, or HM1.24) is a host cellular res

100 The mammalian antiviral membrane protein tetherin (BST2/CD317) can be expressed as two isoforms d

101 Tetherin (BST2/CD317) restricts the release of enveloped

102 Tetherin/Bst2 is an antiviral protein that blocks envelo

103 y not only expands the antiviral spectrum of tetherin but also sheds light on the mechanisms of inter

104 ivity of maRAVV VP40 to restriction by human tetherin but not mouse tetherin.

105 ll-to-cell transmission that is resistant to tetherin but that virion dissemination via plasma is inh

106 ADCC), and conversely that RNAi knockdown of tetherin, but not other cellular proteins down-modulated

107 onstrated that the expression of full-length tetherin, but not the C-terminal glycosylphosphatidylino

108 As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmissio

109 ctivity toward HSV-1 and that the removal of tetherin by Vhs is important for the efficient replicati

110 nmodulation of CD4, but not counteraction of tetherin, by RBF206 Vpu was dependent on the cellular ub

111 Although viral countermeasures against tetherin can differ significantly, overall, tetherin's a

112 While tetherin can mediate virus endocytic uptake and clearanc

113 cluding bone marrow stromal antigen 2 (Bst2)/tetherin/CD317.

114 on localization microscopy revealed that Gag-tetherin coclustering is significantly reduced but persi

115 e can be mediated by tetherin itself or by a tetherin cofactor that promotes uptake of an endocytosis

116 ccurs in the intracellular cisterna and that tetherin colocalizes with HBV virions on the multivesicu

117 through the formation of a ternary SGTA/Vpu/tetherin complex.

118 A deletion in human tetherin confers Nef resistance, representing a hurdle t

119 The long isoform (L-tetherin) contains 12 extra amino acids in its N terminu

120 To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 comple

121 rt codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineag

122 am NF-kappaB activation, indicating that the tetherin cytoplasmic tail resembles the hemi-immunorecep

123 However, transfer of the human tetherin cytoplasmic tail to mouse tetherin restored res

124 ks the first 12 amino acids of the longer (L-tetherin) cytoplasmic tail, which includes a tyrosine mo

125 Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimul

126 examine the role of ATP6V0C in Vpu-mediated tetherin degradation and HIV-1 release, we knocked down

127 that ATP6V0C depletion impairs Vpu-mediated tetherin degradation, resulting in defective HIV-1 relea

128 lates with the ability of Vpu to induce long tetherin degradation.

129 f aspartate at residue 286 liberates NA from tetherin-dependent restriction upon exit from the ER com

130 yrosine residues in the cytoplasmic tails of tetherin dimers.

131 structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmissi

132 cell imaging assay to demonstrate that while tetherin does indeed dramatically reduce cell-free virus

133 ped live-cell imaging assays which show that tetherin does not affect Moloney murine leukemia virus (

134 hese Nef proteins promoted virus release and tetherin downmodulation from the cell surface, and in th

135 ubtype C clones exhibited the lowest CD4 and tetherin downregulation activities, while subtype D and

136 ied Vpu polymorphisms associated with CD4 or tetherin downregulation function and validated six of th

137 ange {IQR}, 0.86 to 1.18]), while the median tetherin downregulation function was moderately lower th

138 elected for Vpu's enhanced targeting of long tetherin during its adaptation to humans.

139 However, the immunological impact of Tetherin during retrovirus infection remains unknown.

140 s by Vpu is not a by-product of CD4 or BST-2/tetherin elimination from the surfaces of infected cells

141 Tetherin encodes an interferon-inducible antiviral prote

142 form specificity reflected a requirement for tetherin endocytosis.

143 ion of alphavirus release requires efficient tetherin endocytosis.

144 hat cell-type-specific cofactors may promote tetherin endocytosis.IMPORTANCE The mechanisms of tether

145 wever, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function.

146 lts show that FIV Envs mediate a distinctive tetherin evasion.

147 Thus, Nef-mediated antagonism of human tetherin evolved prior to the spread of HIV-1 group O an

148 ly evolving species (e.g., coelacanths) does tetherin exhibit sequence similarity to one potential si

149 In addition, GPI anchor-truncated tetherin exhibited a dominant-negative effect and was in

150 Mice encoding endocytosis-competent C57BL/6 Tetherin exhibited lower viremia and pathology at 7 d po

151 monstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insigh

152 We found that surface tetherin expression increased the antibody opsonization

153 observed that overexpression of FLNa reduced tetherin expression levels both on the plasma membrane a

154 ng our transgenic mouse model, we found that tetherin expression on hematopoietic cells resulted in t

155 erved that ATP6V0C overexpression stabilizes tetherin expression.

156 ance cell surface and steady-state levels of tetherin expression.

157 in the lumen of the cisterna membrane under tetherin expression.

158 vacuolar ATPase, ATP6V0C", had no effect on tetherin expression.

159 riction factor and cofactor, as FIV requires tetherin for optimal particle release.

160 IV-enveloped FIV particles actually required tetherin for optimal release from cells.

161 s protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-)

162 etermine the sequence of red-capped mangabey tetherin for the first time and directly demonstrate tha

163 rface of infected cells, while the levels of tetherin forms that restrict were decreased.

164 Tetherin forms that were negative for restriction accumu

165 on, and/or displacement mechanisms to remove tetherin from sites of virus budding.

166 The human tetherin gene can express two isoforms, long and short,

167 ete loss of sequence similarity among modern tetherin genes and their sister genes.

168 We find that tetherin genes in various organisms exhibit no sequence

169 Taken together, our data suggest that tetherin has antiviral activity toward HSV-1 and that th

170 of the HIV-1 accessory factor to antagonize tetherin has been considered to primarily function by li

171 deletion in the cytoplasmic domain of human tetherin, HIV-1 group O, which lacks Vpu-mediated anti-t

172 e developed mice carrying an inducible human tetherin (hTetherin) transgene.

173 Interestingly, RBF206 Vpu counteracts tetherin in a largely species-independent manner, degrad

174 Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo

175 nenveloped capsids, through the induction of tetherin in hepatocyte-derived cells.

176 L-tetherin is more efficient than S-tetherin in inhibiting alphavirus release in 293 cells.

177 vature showed little or no coclustering with tetherin in superresolution analyses.

178 NAD286G-containing proteins associated with tetherin in the endoplasmic reticulum (ER).

179 iretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class

180 f SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner.

181 We investigated the events initiating this tetherin-induced signaling and show that physical retent

182 We now show that Tetherin influences antiretroviral cell-mediated immune

183 Here we show that efficient tetherin inhibition of alphavirus release requires effic

184 owever, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo.

185 BST2/tetherin inhibits the release of enveloped viruses from

186 l domain were not required for either robust tetherin internalization or alphavirus inhibition.

187 Tetherin is a cellular factor that restricts HIV-1 relea

188 BST-2/tetherin is a cellular host factor capable of restrictin

189 Tetherin is a host defense factor that physically preven

190 Tetherin is a host restriction factor that blocks the eg

191 BST-2/CD317/tetherin is a host transmembrane protein that potently i

192 S-tetherin is also reported to be less sensitive to the pr

193 BST-2/Tetherin is an atypical type II transmembrane glycoprote

194 Tetherin is an IFN-inducible transmembrane protein that

195 BST2/tetherin is an innate immune molecule with the unique ab

196 BST-2/tetherin is an interferon-inducible antiviral protein th

197 Tetherin is an interferon-inducible, antiviral host fact

198 t this virus evolved an equilibrium in which tetherin is both restriction factor and cofactor, as FIV

199 This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, indepe

200 Recent evidence shows that tetherin is expressed as two isoforms and that Vpu prefe

201 Similarly, BST-2/Tetherin is first exposed to the cytosol as a dimeric ox

202 L-tetherin is more efficient than S-tetherin in inhibiting

203 The structure helps explain why human tetherin is Nef-resistant and why lentiviruses that succ

204 Moreover, tetherin is part of a cluster of three potential sister

205 broad range of targets, we hypothesized that tetherin is recruited through conserved features shared

206 riments revealed that the ATP6V0C-stabilized tetherin is sequestered in a CD63- and lysosome-associat

207 tion studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternar

208 of the HIV-1 Vpu protein to counteract human tetherin is thought to have been one of the key events i

209 Tetherin/BST-2 (here called tetherin) is an antiviral protein that restricts release

210 ation, the ability of Vpu to counteract BST2/tetherin, is associated with the evolution of simian imm

211 uses to counteract a host antiviral protein, tetherin, is strictly maintained.

212 the enhanced ability to counteract the long tetherin isoform is conserved among HIV-1 strains that m

213 c HIV-1 group N, do not discriminate between tetherin isoforms.

214 o not encode an antagonist for either of the tetherin isoforms.

215 hat this endocytic uptake can be mediated by tetherin itself or by a tetherin cofactor that promotes

216 ntly lower in wild-type C57BL/6 mice than in Tetherin knockout mice at 2 wk postinfection, and antire

217 the co-stimulatory molecule CD80 compared to Tetherin KO DCs.

218 FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs.

219 vels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite r

220 As human tetherin lacks DIWK, antagonism of tetherin by Nef is a

221 The shorter isoform of the human protein (S-tetherin) lacks the first 12 amino acids of the longer (

222 did not reduce intracellular or cell surface tetherin levels.

223 FIV Env might exclude tetherin locally or direct assembly to tetherin-negative

224 adaptive immunity, the antiviral activity of tetherin may be augmented by virus-specific antibodies,

225 This study advances our understanding of tetherin-mediated HIV-1 restriction by defining the spat

226 Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) r

227 ht into the biophysical mechanism underlying tetherin-mediated restriction of HIV-1, we utilized cryo

228 HIV-1-infected cells to ADCC as a result of tetherin-mediated retention of budding virions on the ce

229 Together, our results suggest that tetherin-mediated virus internalization plays an importa

230 Distance measurements support the extended tetherin model, in which the coiled-coil ectodomains are

231 ength, which is consistent with the extended tetherin model.

232 g the spatial arrangement and orientation of tetherin molecules at sites of HIV-1 restriction.

233 The precise arrangement of tetherin molecules at the plasma membrane site of HIV-1

234 Native immunogold labeling showed tetherin molecules located on HIV-1 VLPs and virions in

235 st, in U-2 OS cells, the YXY motif and the L-tetherin N-terminal domain were not required for either

236 clude tetherin locally or direct assembly to tetherin-negative membrane domains.

237 ns unclear whether SIVrcm Nef can antagonize tetherin of its natural host.

238 viral spread by downregulating CD4 and BST-2/tetherin on the surface of infected cells.

239 were both highly correlated to the levels of tetherin on the surfaces of infected primary CD4 T cells

240 Finally, knockdown of tetherin or overexpression of dominant negative tetherin

241 SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that o

242 marrow stromal cell Ag 2 (BST2, aka HM1.24, tetherin, or CD317) is expressed by different cell types

243 cantly greater increase in the expression of tetherin (P = 0.003) and TRIM22 (P = 0.0006) in response

244 del substrates (NS1, NHK-alpha1AT, and BST-2/Tetherin), p97 and YOD1 are required in the downstream e

245 ge to the actin cytoskeleton likely triggers tetherin phosphorylation and subsequent signal transduct

246 RICH2 (ARHGAP44), and a naturally occurring tetherin polymorphism with reduced RICH2 binding exhibit

247 However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVc

248 The restriction factor BST2 (tetherin) prevents the release of enveloped viruses from

249 Here we characterized tetherin proteins of species representing both branches

250 feron (IFN-alpha) levels in plasma, and that tetherin remains above baseline levels throughout chroni

251 to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels, and

252 Tetherin represents an important barrier for successful

253 The antiviral function of tetherin requires the carboxyl-terminal GPI anchor, whil

254 us type 1 vpu or siRNA-mediated depletion of tetherin rescued budding capabilities in these proteins.

255 the human tetherin cytoplasmic tail to mouse tetherin restored restriction of maRAVV VP40.

256 nterferon-stimulated genes (ISGs), ISG20 and tetherin, restrict HBV spread in NTCP-expressing hepatom

257 We determined that tetherin-restricted HIV-1 virions were physically connec

258 ically modulates the ability of NA to escape tetherin restriction at the plasma membrane and results

259 xact mechanism of Vpu-mediated antagonism of tetherin restriction remains to be fully understood.

260 The HIV-1 accessary protein Vpu counteracts tetherin restriction via sequestration, down-regulation,

261 tein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in con

262 ne transport partly by mediating escape from tetherin restriction.

263 Tetherin restricts alphaviruses, which are highly organi

264 portance of these observations, knockdown of tetherin resulted in a 1-1.5 log increase in influenza v

265 The type I interferon-inducible factor tetherin retains virus particles on the surfaces of cell

266 rin endocytosis.IMPORTANCE The mechanisms of tetherin's antiviral activities and viral tetherin antag

267 tetherin can differ significantly, overall, tetherin's antiviral activity correlates with physical t

268 lammatory signaling, play key roles in human tetherin's antiviral function in vivo.

269 L-tetherin's inhibition of alphavirus release correlated w

270 Tetherin serves as an innate sensor of viral infection i

271 Retroviral-induced tetherin signaling is coupled to the cortical actin cyto

272 Because the SGTA-stabilized tetherin species is partially localized to the cytosol,

273 cytosolic accumulation of a non-glycosylated tetherin species.

274 relocalization of a 23-kDa, non-glycosylated tetherin species.

275 s (HIV-1 and HIV-2) had to evolve novel anti-tetherin strategies.

276 Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires fun

277 ses due to the absence of sequences in human tetherin that confer susceptibility to Nef.

278 eficiency viruses to overcome restriction by tetherin, this activity was acquired by the Vpu protein

279 VR receptors and the host restriction factor tetherin, this antagonism is carried out via direct inte

280 homooligomerization of this protein, and the tetherin TMD forms homodimers.

281 M Nef may acquire the ability to counteract tetherin to compensate for the loss of this function by

282 terferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication.

283 We show that the reduced sensitivity of S-tetherin to HIV-1 Vpu is a feature of all group M protei

284 jacks the FLNa function in the modulation of tetherin to neutralize the antiviral factor tetherin.

285 this deletion to inhibit transport of human tetherin to the cell surface, enhances virion release, a

286 We generated a mouse model with an inducible tetherin transgene in order to study how tetherin affect

287 ciates with tetherin and that FLNa modulates tetherin turnover.

288 Na, but not FLNb, plays an essential role in tetherin turnover.

289 up M HIV-1 Vpu primarily adapted to target L-tetherin upon zoonotic transmission from chimpanzees, an

290 induced retro-translocation of CD4 and BST-2/Tetherin using our novel biotinylation technique in livi

291 es the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif.

292 The YXY motif in L-tetherin was necessary for alphavirus restriction in 293

293 Vpu clone to downregulate endogenous CD4 and tetherin was quantified using flow cytometry following t

294 mal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell gr

295 contrast to the direct antiviral effects of Tetherin, which are dependent on cell surface expression

296 lammatory signaling by the host protein BST2/tetherin, which is mediated by the transcription factor

297 ed to counteract an antiviral protein called tetherin, which may selectively inhibit cell-free virus

298 BTV16 also induced the expression of tetherin, which restricts HIV release from infected cell

299 lowest ability to downregulate both CD4 and tetherin, while subtype B and D clones were more functio

300 HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and