ライフサイエンスコーパス: XMRV

1 XMRV DNA was not detected in any participant samples.

2 XMRV established a persistent, chronic disseminated infe

3 XMRV infection was associated with prostate cancer, espe

4 XMRV infection was demonstrated in the virus-injected do

5 XMRV is detectable in normal and tumor prostate tissue f

6 XMRV proteins were expressed primarily in malignant epit

7 XMRV proviral genomes in LNCaP and DU145 cells were hype

8 XMRV proviral genomes were extensively hypermutated upon

9 XMRV provirus integration sites were mapped in DNA isola

10 XMRV replication in the prostate cancer cell line DU145

11 XMRV RT is highly susceptible to some nucleoside RT inhi

12 XMRV shows at most 94% identity to known mouse retroviru

13 XMRV transmission was evaluated by whole-blood transfusi

14 XMRV was detected in 32 (22%) of the 144 patients.

15 XMRV was first identified in prostate stromal cells surr

16 XMRV was not present in any of the mouse strains tested,

17 the prostate cell line DU145 after an acute XMRV infection and compared the integration site pattern

18 In addition, XMRV poorly infects NIH 3T3 cells expressing human Xpr1

19 Additionally, XMRV integration sites in cancer tissues were associated

20 resistant to the effects of IFN-beta against XMRV.

21 ce mounted adaptive immune responses against XMRV, as evidenced by the production of neutralizing and

22 ted findings of near-genetic identity of all XMRVs, we identified a genetically diverse group of MLV-

23 Among all retroviruses analyzed, XMRV has the strongest preference for transcription star

24 We found XMRV DNA in 6% and XMRV protein expression in 23% of prostate cancers.

25 nsitivities to specific X/P-MLV isolates and XMRV.

26 associated with integration by both MLV and XMRV.

27 .R, were shown to be infectable by X-MLV and XMRV; these strains carry different alleles at Fv1 and v

28 etroviruses, gag gene expression of MuLV and XMRV depends on post-transcriptional regulation mediated

29 MuLV and XMRV PTE share 98% identity and have highly similar RNA

30 and immunohistochemistry (IHC) with an anti-XMRV specific antiserum.

31 V, we are unable to verify the antibodies as XMRV specific.

32 43 of whom had previously been identified as XMRV-positive.

33 d from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy dono

34 To help elucidate the mechanisms behind XMRV infection, we show that prostatic fibroblast cells

35 he growing view that the association between XMRV and CFS likely reflects contamination of laboratori

36 The association between XMRV and chronic fatigue has proved to be controversial.

37 We found no association between XMRV and patients with chronic fatigue syndrome or chron

38 syndrome, suggesting an association between XMRV infection and these two diseases.

39 spite extensive sequence differences between XMRV and the intensively studied Moloney murine leukemia

40 resumably generated by recombination between XMRV and host cell nucleic acids.

41 Neither a casual relationship between XMRV infection and prostate cancer nor a mechanism of tu

42 uggesting common transmission routes between XMRV and HIV-1, HIV-1 infected individuals may represent

43 ls expressing the appropriate receptors bind XMRV or GALV envelope proteins.

44 ptor 1 allowed these cells to be infected by XMRV.

45 data demonstrate infection of Mus pahari by XMRV, potential cell tropism of the virus, and immunolog

46 purporting to show that a retrovirus called XMRV (xenotropic murine leukemia virus-related virus) wa

47 ection, may play important roles in defining XMRV tropisms in certain cell types.

48 creased long terminal repeat (LTR)-dependent XMRV transcription.

49 re experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cel

50 whereas the two other assays did not detect XMRV in any specimen.

51 at current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening

52 ver, other articles report failure to detect XMRV in PCa.

53 s, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody.

54 We detected XMRV infection in the two cell lines and in the later pa

55 sequences of Xpr1 are required for efficient XMRV entry.

56 t cells, respectively, can mediate efficient XMRV or GALV infection.

57 onstrate that TNF-alpha and EBV LMP1 enhance XMRV replication in prostate carcinoma and B-lineage cel

58 SEVI enhanced XMRV infectivity but did not bypass the requirement for

59 te of the intravenous inoculation, extensive XMRV replication was noted in prostate during acute but

60 chain reaction techniques, but did not find XMRV or multiple other common viruses, suggesting that e

61 We did not find XMRV or related MLVs either as viral sequences or infect

62 le source of contamination in PCR assays for XMRV.

63 nor and recipient monkeys were evaluated for XMRV infection by nested PCR assays with nucleotide sequ

64 No evidence for XMRV in PCa was obtained in these experiments.

65 ividuals may represent a high-risk group for XMRV infection and spread.

66 support the use of Mus pahari as a model for XMRV pathogenesis and as a platform for vaccine and drug

67 hether Mus pahari could serve as a model for XMRV, primary Mus pahari fibroblasts and mice were infec

68 x), and yellow fever virus were negative for XMRV and highly related MLV sequences.

69 All healthy blood donors were negative for XMRV proviral sequences.

70 enuated human vaccines using generic PCR for XMRV and MLV sequences.

71 gnificantly more likely to test positive for XMRV in both tumor and normal tissue rather than either

72 ory mice lack a functional XPR1 receptor for XMRV and are therefore not a suitable model for the viru

73 idence show that the cell entry receptor for XMRV, Xpr1, mediates this effect, and chemical cross-lin

74 essed the human Xpr1 cell entry receptor for XMRV.

75 important cellular determinants required for XMRV entry into different human prostate cells in vitro,

76 A positive result for XMRV was not significantly correlated with the R462Q pol

77 finding increases the population at risk for XMRV infection from only those homozygous for the RNASEL

78 fense protein RNase L, suggesting a role for XMRV in prostate carcinogenesis.

79 ranting further study of a possible role for XMRV integration in carcinogenesis.

80 allelic discrimination and were screened for XMRV proviral DNA by nested polymerase chain reaction sp

81 DNA was screened for XMRV provirus with two sensitive, published PCR assays t

82 ic stromal fibroblasts, a recent study found XMRV protein antigens mainly in malignant prostate epith

83 We found XMRV DNA in 6% and XMRV protein expression in 23% of pro

84 We found XMRV infection to be independent of a common polymorphis

85 blasts and mice were infected with cell-free XMRV.

86 of adenylate cyclase rescued the cells from XMRV toxicity, indicating that toxicity resulted from re

87 Furthermore, XMRV Gag was detected in tissues throughout, with wide d

88 Furthermore, XMRV RNA was detected in prostatic secretions of some me

89 ssociation between the human gammaretrovirus XMRV and chronic fatigue syndrome.

90 esized that an understanding of when and how XMRV first arose might help explain the discrepant resul

91 ells and B cells, we sought to determine how XMRV evades suppression of replication by APOBEC3 protei

92 However, XMRV has not been found in prostate carcinoma cells.

93 hat results interpreted as evidence of human XMRV infection reflect laboratory contamination rather t

94 eins restrict XMRV infection in vitro, human XMRV infection, if it occurred, would be expected to be

95 ly augmented viral Gag protein production in XMRV-infected cells.

96 Infection of cells in vitro resulted in XMRV Gag expression and the production of XMRV virions.

97 tween CFS and MLV-related viruses, including XMRV, and the off-label use of antiretrovirals for the t

98 prostatic acid phosphatase greatly increase XMRV infections of primary prostatic epithelial and stro

99 t NF-kappaB activation can markedly increase XMRV production.

100 However, infectious XMRV could be recovered from the infected PBMCs by cocul

101 an potentially act as a source of infectious XMRV for spread to cells that express low levels of host

102 However, the recovery of infectious XMRV from human PBMCs suggested that XMRV can replicate

103 cells, may be ideal producers of infectious XMRV.

104 which are expressed in human PBMCs, inhibit XMRV in transient-transfection assays involving a single

105 dentified RNA aptamers that potently inhibit XMRV, but not HIV-1 RT.

106 Here we constructed a full-length XMRV genome from prostate tissue RNA and showed that the

107 ived from a xenotropic retrovirus that, like XMRV, employs Xpr1 as a receptor, and also by vectors be

108 rus were minimal in a variety of cell lines, XMRV displayed robust expression and infection in LNCaP

109 ults indicate that previous evidence linking XMRV and MLVs to CFS is likely attributable to laborator

110 neal injection of XMRV into Mus pahari mice, XMRV proviral DNA could be detected in spleen, blood, an

111 h undetectable in blood after about a month, XMRV viremia was reactivated at 9 months, confirming the

112 A mutant XMRV with a mutation at the kappaB-1 site replicated sig

113 BHK cells bind neither XMRV nor GALV envelope proteins.

114 Nevertheless, XMRV is a retrovirus of undefined pathogenic potential t

115 murine leukemia viruses (MLVs), most notably XMRV [xenotropic murine leukemia virus (X-MLV)-related v

116 RV in cell culture, we tested the ability of XMRV to spread and replicate in various prostate and non

117 LUSIONS/SIGNIFICANCE: The virtual absence of XMRV in PBMCs suggests that XMRV is not associated with

118 -SS, respectively) with different amounts of XMRV and monitored virus production by using quantitativ

119 Analyses of XMRV integration sites in tissues from prostate cancer p

120 vidence for contamination during analysis of XMRV integration sites.

121 our results suggest that the association of XMRV with human disease is due to contamination of human

122 tions provide evidence for an association of XMRV with malignant cells and with more aggressive tumor

123 cells with at least 10 integrated copies of XMRV, warranting further study of a possible role for XM

124 ugh it now seems clear that the detection of XMRV in humans was the result of sample contamination wi

125 Detection of XMRV was confirmed by DNA sequencing.

126 ential, kinetics, and tissue distribution of XMRV in an animal model, we inoculated five macaques wit

127 ulation with >10(10) RNA copy equivalents of XMRV, viral replication was limited and transient, peaki

128 In summary, the establishment of XMRV infection in patients may be dependent on infection

129 We found no evidence of XMRV and MLV in eight live attenuated human vaccines fur

130 While that study showed evidence of XMRV infection exclusively in the prostatic stromal fibr

131 We found no evidence of XMRV or other MLVs in these blood samples.

132 Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disa

133 We found that although the expression of XMRV viral proteins and the spread of infectious virus w

134 bination event that led to the generation of XMRV could have occurred only in the laboratory.

135 the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiv

136 cell line, and we observed hypermutation of XMRV genomes in PBMCs.

137 these results suggest that hypermutation of XMRV in human PBMCs constitutes one of the blocks to rep

138 Furthermore, hypermutation of XMRV proviruses at GG dinucleotides may be a useful and

139 in their virion incorporation, inhibition of XMRV replication, and G-to-A hypermutation of the viral

140 ere partially resistant to IFN inhibition of XMRV.

141 After intraperitoneal injection of XMRV into Mus pahari mice, XMRV proviral DNA could be de

142 ines as a possible source of introduction of XMRV and MLV into human populations.

143 The study demonstrates the lack of XMRV transmission by whole-blood transfusion during the

144 and compared the integration site pattern of XMRV with those found for murine leukemia virus and two

145 etermine the integration site preferences of XMRV and the potential risk of proviral insertional muta

146 The presence of XMRV in normal tissue suggests that infection may preced

147 thy donors were screened for the presence of XMRV-reactive antibodies by Western blot.

148 in XMRV Gag expression and the production of XMRV virions.

149 The U3 promoter of XMRV and a glucocorticoid response element (GRE) within

150 last cells express Xpr1, a known receptor of XMRV, but its expression is absent in other cell lines o

151 ppaB-1 and kappaB-2) in the LTR U3 region of XMRV and demonstrated that both sites bind to the NF-kap

152 plete copy, we did find a 3,600-bp region of XMRV in an endogenous retrovirus present in NIH/3T3 cell

153 een, suggesting intracellular restriction of XMRV infection by APOBEC3 in vivo.

154 s and supporting the possible restriction of XMRV replication in humans by a similar mechanism.

155 important insights into the possible role of XMRV as an etiologic agent in human prostate cancer.

156 Given the sequence similarity of XMRV to mink cell focus-forming (MCF) viruses and the en

157 gest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with

158 search for a more closely related source of XMRV in mice.

159 e of the blocks to replication and spread of XMRV.

160 ating little or no replication and spread of XMRV.

161 In this forum, we discuss the story of XMRV and how we can apply lessons learned here to inform

162 ous studies have found little to no trace of XMRV in different human cohorts.

163 oth spliced and unspliced RNA transcripts of XMRV and MLV, resulting in their nuclear retention or de

164 d raltegravir may be useful for treatment of XMRV infection.

165 To determine the tropism of XMRV in cell culture, we tested the ability of XMRV to s

166 use endogenous retroviruses than to those of XMRVs and were even less closely related to those of eco

167 the effects of dihydrotestosterone (DHT) on XMRV transcription and replication.

168 of receptor-expressing BHK cells to GALV or XMRV, as shown by tunicamycin treatment and mutation of

169 oviruses were strongly (X-MLV) or partially (XMRV) susceptible to inactivation by sera from CFS patie

170 ell lines CWR22Rv1 and CWR-R1, which produce XMRV virtually identical to the viruses recently found i

171 wed that all were infected with and produced XMRV, and one produced a highly active transforming viru

172 leading to NF-kappaB activation may promote XMRV spread in humans.

173 patients in the original study that reported XMRV in CFS patients.

174 pes of the RNASEL gene, which could restrict XMRV infection, may play important roles in defining XMR

175 Given that human APOBEC proteins restrict XMRV infection in vitro, human XMRV infection, if it occ

176 tumor cells were required for the resulting XMRV recombinant to infect and propagate.

177 oma cells infected with the human retrovirus XMRV (xenotropic murine leukemia virus-related virus) ca

178 The human retrovirus XMRV (xenotropic murine leukemia virus-related virus) is

179 The human retrovirus XMRV (xenotropic murine leukemia virus-related virus) is

180 The retrovirus XMRV (xenotropic murine leukemia virus-related virus) ha

181 ort, "Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue sy

182 Both antisera always stained XMRV-infected or -transfected cells, but never stained c

183 Furthermore, DHT stimulated XMRV replication 3-fold, whereas androgen inhibitors (ca

184 mulation with dihydrotestosterone stimulated XMRV-LTR-dependent transcription in 293T cells, and the

185 establish a nonhuman primate model to study XMRV replication/dissemination, transmission, pathogenes

186 Although we found strong evidence to support XMRV infection of prostatic fibroblast cell lines via Xp

187 Surprisingly, XMRV infection showed organ-specific cell tropism, infec

188 wo sensitive, published PCR assays targeting XMRV gag and env and one sensitive, published nested PCR

189 d the presence of a gammaretrovirus, termed "XMRV" (xenotropic murine leukemia virus-related virus) i

190 ukemogenic activity of the latter, we tested XMRV for related MCF-like cytopathic activities in cultu

191 We conclude that XMRV was not present in the original CWR22 tumor but was

192 present the evidence for our contention that XMRV is not a human pathogen.

193 Our studies demonstrate that XMRV is a virus that has infected humans and is suscepti

194 pre-steady state kinetics demonstrated that XMRV RT is significantly less efficient in DNA synthesis

195 We demonstrated that XMRV RT mutants K103R and Q190M, which are equivalent to

196 We provide experimental evidence that XMRV is indeed a gammaretrovirus with protein compositio

197 We found that XMRV efficiently replicated in CEM-SS cells and viral pr

198 potential disease mechanisms, we found that XMRV infection induced apoptosis in SY5Y human neuroblas

199 elial cell lines to test the hypothesis that XMRV might have direct transforming activity but found o

200 These results indicate that XMRV has no direct transforming activity but can activat

201 These findings indicate that XMRV replication and spread were limited in pigtailed ma

202 in abundance by the prostate indicates that XMRV replication occurs in an environment that provides

203 roblast cell lines via Xpr1, we learned that XMRV was indeed capable of infecting cells that did not

204 We also observed that XMRV replication was susceptible to the nucleoside rever

205 These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of

206 It is possible that XMRV is not actually circulating in the human population

207 tics of mismatch incorporation revealed that XMRV RT has higher fidelity than HIV-1 RT.

208 These results show that XMRV can generate acutely transforming viruses at a low

209 As part of these experiments, we show that XMRV can infect and be produced at a high titer from hum

210 These results show that XMRV has clear ancestors in mice and highlight another p

211 Our groups recently showed that XMRV was created through recombination between two endog

212 T3 cells expressing human Xpr1, showing that XMRV is a B-tropic virus and that its infectivity is reg

213 that express TRIM5alpha (Ref1), showing that XMRV is resistant to TRIM5alpha restriction.

214 These data suggest that XMRV may replicate more efficiently in LNCaP cells in pa

215 ectious XMRV from human PBMCs suggested that XMRV can replicate in these cells despite the expression

216 ant to the respective drugs, suggesting that XMRV can acquire resistance to these compounds through t

217 rtual absence of XMRV in PBMCs suggests that XMRV is not associated with HIV-1 infected or HIV-1/HCV

218 s showed that the PCR assay could detect the XMRV in a single infected cell, even in the presence of

219 Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but o

220 neage cells through the kappaB-1 site in the XMRV LTR, suggesting that inflammation, EBV infection, a

221 Findings suggest that integration of the XMRV long terminal repeat (LTR) into host DNA could impa

222 The transcriptional activity of the XMRV long terminal repeat (LTR) was found to be higher t

223 , we determined the dimeric structure of the XMRV packaging domain, examined dynamic interactions bet

224 lls produced by fusing BHKXpr1 or BHKPiT1 to XMRV- or GALV-resistant cells, respectively, can mediate

225 elope proteins, suggesting that the block to XMRV and GALV infection is mediated at the level of enve

226 he Xpr1(n) receptor variant nonpermissive to XMRV and xenotropic murine leukemia virus (X-MLV) infect

227 ed isolated incidents of serum reactivity to XMRV, we are unable to verify the antibodies as XMRV spe

228 0%) from healthy donors showed reactivity to XMRV-infected cell lysate.

229 arly identical in properties and sequence to XMRV isolated by others and consist primarily of a singl

230 ropean mice, making it unlikely that the two XMRV ancestors could have recombined independently in th

231 ficantly less efficiently than the wild-type XMRV in the prostate carcinoma LNCaP, DU145, and PC-3 ce

232 Here we used XMRV-specific PCR to search for a more closely related s

233 nkeys based upon PCR analysis of PBMCs using XMRV-specific gag and env primers, Western blot analysis

234 (MLV) and xenotropic murine leukemia virus (XMRV), named the CAE (cytoplasmic accumulation element).

235 otropic murine leukemia virus-related virus (XMRV) among 293 participants seen at academic hospitals

236 otropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-relat

237 otropic murine leukemia virus-related virus (XMRV) has been found in the prostatic tissue of prostate

238 otropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and

239 otropic murine leukemia virus-related virus (XMRV) has recently been detected in prostate cancer tiss

240 otropic murine leukemia virus-related virus (XMRV) in human tissue samples has been shown to be due t

241 otropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and its associati

242 otropic murine leukemia virus-related virus (XMRV) in peripheral blood mononuclear cells (PBMCs) from

243 c murine leukemia virus (MLV)-related virus (XMRV) in prostate cancer and chronic fatigue syndrome re

244 otropic murine leukemia virus-related virus (XMRV) infection was incorrectly associated with prostate

245 otropic murine leukemia virus-related virus (XMRV) integration site sequences previously identified f

246 otropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus found in association with hum

247 otropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus linked to prostate carcinoma

248 otropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus originally identified in a su

249 otropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus recently isolated from human

250 otropic murine leukemia virus-related virus (XMRV) is a new human gammaretrovirus identified in prost

251 otropic murine leukemia virus-related virus (XMRV) is a novel human gammaretrovirus discovered in ass

252 xenotropic murine retrovirus-related virus (XMRV) or gibbon ape leukemia virus (GALV) infection, eve

253 otropic murine leukemia virus-related virus (XMRV) was first identified in human prostate cancer tiss

254 Xenotropic murine leukemia-related virus (XMRV) was identified in association with human prostate

255 otropic murine leukemia virus-related virus (XMRV) was previously reported to be associated with huma

256 otropic murine leukemia virus-related virus (XMRV) was recently discovered in human prostate cancers

257 otropic murine leukemia virus-related virus (XMRV), a gammaretrovirus that can infect human cells.

258 otropic murine leukemia virus-related virus (XMRV), a gammaretrovirus, has been isolated from human p

259 tropic murine leukaemia virus-related virus (XMRV), a gammaretrovirus, was discovered in prostate can

260 otropic murine leukemia virus-related virus (XMRV), and isolated 32,585 unique integration sites usin

261 otropic murine leukemia virus-related virus (XMRV), has been identified in patients with prostate can

262 Vs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatig

263 otropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 2

264 s, xenotropic murine leukemia-related virus (XMRV), in blood; other studies could not replicate this

265 otropic murine leukemia virus-related virus (XMRV), in prostate cancer tissue from patients homozygou

266 otropic murine leukemia virus-related virus (XMRV)-has recently been shown to be strongly associated

267 otropic murine leukemia virus-related virus (XMRV).

268 To determine whether XMRV can replicate and spread in cultured PBMCs even tho

269 We therefore investigated whether XMRV infection could be found in patients with prostate

270 results are consistent with a model in which XMRV may contribute to tumorigenicity via a paracrine me

271 PBMC) DNA preparations are contaminated with XMRV plasmid DNA.

272 PreXMRV-2, which share 99.92% identity with XMRV over >3.2-kilobase stretches of their genomes.

273 Monkeys were infected with XMRV to serve as donor monkeys for blood transfers at we

274 aca nemestrina) experimentally infected with XMRV.

275 imal model, we inoculated five macaques with XMRV intravenously.

276 cy chimeric virus particles pseudotyped with XMRV envelope protein were used to demonstrate that the

277 escent protein (GFP) vector pseudotyped with XMRV produced GFP(+) CD4(+) T cells and CD19(+) B cells.