ライフサイエンスコーパス: provirus

1 s into the host-cell genome to establish the provirus.

2 sors to the primer binding site (PBS) of the provirus.

3 intermediates in cells expressing the HIV-1 provirus.

4 n to regulate the transcription of the HIV-1 provirus.

5 with recognizable hallmarks of an integrated provirus.

6 infections plus an agent to activate latent provirus.

7 ks viral replication but cannot purge latent provirus.

8 ads to hypermutation and inactivation of the provirus.

9 spread in tumor cells containing integrated provirus.

10 nscripts were identified covering the entire provirus.

11 els similar to those in cells containing one provirus.

12 olymerase II transcription of the integrated provirus.

13 enomic features of the host DNA flanking the provirus.

14 duced this sequence into an infectious HIV-1 provirus.

15 distribution of RNA polymerase II in the HIV provirus.

16 ion as well as silencing of the latent HIV-1 provirus.

17 nscription as well as reactivation of latent provirus.

18 generation of infectious progeny virus from provirus.

19 to harbor full-length, replication-competent provirus.

20 omoter-driven transcription of an integrated provirus.

21 genetic structure of the gag region in each provirus.

22 anded CD4(+) T-cell clone contains an intact provirus.

23 ts integrated into the host cell genome as a provirus.

24 require prior establishment of an integrated provirus.

25 ing CpG-rich IAP (intracisternal A particle) proviruses.

26 y expanded cells carry replication-competent proviruses.

27 rimarily in CD4(+) T cells containing silent proviruses.

28 hat, in vitro, results in a higher number of proviruses.

29 and nonhuman primate cells expressing HIV-1 proviruses.

30 ies exist to selectively activate latent HIV proviruses.

31 packaging and virus titer in the context of proviruses.

32 cantly alter the expression of the remaining proviruses.

33 Tat protein leads to the activation of K111 proviruses.

34 ed, not a single mouse carried both parental proviruses.

35 mologues in prokaryotic cells, outside known proviruses.

36 tient and potential cell line sources of the proviruses.

37 ynthesis induced up to 40% of the latent HIV proviruses.

38 eting cells with specific types of defective proviruses.

39 due to limited or broad activation of HIV-1 proviruses.

40 of transcription from an extensive range of proviruses.

41 RTs extended mismatches in more than 90% of proviruses.

42 termined by the number of genetically intact proviruses.

43 o successful therapy to eradicate integrated proviruses.

44 We show that three HML-2 proviruses-6q25.1, 8q24.3, and 19q13.42-are upregulated

45 Here we show that defective proviruses accumulate rapidly within the first few weeks

46 ecipitation (ChIP) assays showed that latent proviruses accumulate RNA polymerase II (RNAP II) on the

47 5, X4, and R5/X4), six primary isolates, and provirus-activated ACH-2 cells examined.

48 laboratory strains and primary isolates) and provirus-activated latently infected cells.

49 Abs in triggering ADCML of HIV-1 virions and provirus-activated latently infected cells.

50 of antiretroviral therapy with RCA blockage, provirus activators, and therapeutic vaccines may repres

51 potentially containing replication-competent proviruses, along with evidence of continuing virus prod

52 as well as the distribution of both parental proviruses among different mouse species, are described.

53 transcriptional silencing of the integrated provirus and driven, at least in part, by histone deacet

54 Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4

55 scription originating outside and inside the provirus and identified the vector sequences contributin

56 ike properties (TSCM) that harbor infectious provirus and that likely contribute to HIV-1 persistence

57 firmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessar

58 transcriptional quiescence of the integrated provirus and the circumvention of immune defense mechani

59 TAM-containing proteins, one encoding a MMTV provirus and the other a B cell receptor fusion protein.

60 lentiviral vectors, yet fail to integrate as proviruses and are instead converted into episomal circl

61 ased methods, we identified seven CrERVgamma proviruses and demonstrated that they show various level

62 s (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs).

63 the MT-2 cell line, which harbors truncated proviruses and expresses aberrant forms of the Gag prote

64 that BVs are transmitted only vertically as proviruses and produce replication-defective virions tha

65 Viral RNA arose from complete proviruses and proviruses devoid of a 5' long terminal r

66 fected cells harboring replication-competent proviruses and residual viremia.

67 to use the relationship between full-length proviruses and solo-LTRs to help identify large scale co

68 clonally expanded T cells contain defective proviruses and that the replication-competent reservoir

69 nt at high levels at the LTR of silenced HIV proviruses and was rapidly displaced following proviral

70 IFN-stimulated response element within HIV-1 provirus, and it is displaced following T cell activatio

71 ation of T cells harboring latent integrated provirus, and recent studies indicate that proliferation

72 anded clones can carry replication-competent proviruses, and cells from these clones can release infe

73 e genus Bracovirus (BVs) persist in wasps as proviruses, and their genomes consist of two functional

74 Remarkably, K111 proviruses appear in the genomes of the extinct Neandert

75 Importantly, antigens derived from this provirus are immunogenic, stimulating cytotoxic T cells

76 Sequence reads that contain a provirus are mapped to the human genome, sequence reads

77 ndividuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent

78 The majority of HIV-1 proviruses are defective and considered clinically irrel

79 That the vast majority of proviruses are defective clouds our assessment of the de

80 +)T cells are clonally expanded; most of the proviruses are defective.

81 chronic infection, and in this setting, most proviruses are defective.

82 dogenous retrovirus group K (HERV-K) (HML-2) proviruses are expressed at significantly higher levels

83 al cells of the oral mucosa, although latent proviruses are found in most, if not all, tissues.

84 The noninduced proviruses are generally considered defective but have n

85 cell activation reverses latency, but <1% of proviruses are induced to release infectious virus after

86 No extant CERV1 and -2 proviruses are known to encode functional proteins.

87 se results reveal that the majority of HIV-1 proviruses are not reactivated by current therapeutic ap

88 of the 91 currently annotated HERV-K (HML-2) proviruses are regulated by Tat.

89 Human endogenous retrovirus type K (HERV-K) proviruses are scattered throughout the human genome, bu

90 Latent HIV proviruses are silenced as the result of deacetylation a

91 Latent human immunodeficiency virus (HIV) proviruses are thought to be primarily reactivated in vi

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

93 The extent to which the HERV-K (HML-2) proviruses become activated and the nature of their acti

94 PDVs persist in wasps as integrated proviruses but are packaged as circularized and segmente

95 + T cells that contain replication-competent provirus, but exhibit little or no active viral gene exp

96 ins and wild mouse species for an endogenous provirus, Bxv1, that is capable of producing infectious

97 t-mediated transactivation of the integrated provirus by binding specifically to the TAR-binding doma

98 pharmaceutical reactivation of dormant HIV-1 proviruses by histone deacetylase inhibitors (HDACi) rep

99 Thus, CTLs may change the landscape of HIV-1 proviruses by preferentially targeting cells with specif

100 duce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic

101 defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced

102 limits in vivo expression of germ line X-MLV proviruses capable of producing infectious virus.

103 have identified the presence of "defective" proviruses capable of transcribing novel unspliced HIV-R

104 The level of integration (proviruses/cell) in naive cells was lower than that in m

105 elics of ancient integration events, "young" proviruses competent for retrotransposition-found in man

106 Further, cells with proviruses containing lethal mutations upstream of CTL e

107 ess likely to be found among highly expanded provirus-containing cell clones.

108 The resulting provirus contains identical 5' and 3' peripheral long te

109 Viral RNA arose from complete proviruses and proviruses devoid of a 5' long terminal repeat, suggesti

110 Using isogenic tier 1 or tier 2 proviruses differing only in the 3N mutation, we showed

111 The NL4-3 YRHHY>A5 and NL4-3 DRMR>A4 mutant proviruses displayed G-to-A hypermutations primarily in

112 novel, independent mutant in which a single provirus disrupted one allele of the gene encoding the s

113 Low levels of HTLV-2 provirus DNA were detected in the blood, lymphoid tissue

114 over, unrepaired rNMPs incorporated into the provirus during HIV-1 reverse transcription would be gen

115 ccumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unkn

116 perienced no frequency increase in X4-tropic proviruses during therapy.

117 or but was generated by recombination of two proviruses during tumor passaging in mice.

118 h indicates a preferential tropism-dependent provirus elimination in the immunocompetent host.

119 viral plus-strand DNA transfer and inhibits provirus establishment in the host genome.

120 n vivo, and cells with replication competent proviruses expand and survive because only a small fract

121 Gag act during immature capsid formation in provirus-expressing cells.

122 cell chromatin that underlie integration and provirus expression are poorly understood.

123 omosomes, thus maximizing the probability of provirus expression immediately after integration.

124 RNAP II promoter proximal pausing and limits provirus expression in HIV-infected primary CD4(+) T cel

125 human endogenous retrovirus group K (HERV-K) provirus expression plays a role in the pathogenesis of

126 , there was less than 5% induction of latent proviruses following knockdown of SUV39H1, which is requ

127 step to reverse post-integrated latent HIV-1 proviruses for purging of reservoir cells.

128 whether A3F similarly interferes with HIV-1 provirus formation.

129 for A3G than A3F function in blocking HIV-1 provirus formation.

130 NA synthesis, at the step of 2LTR circle and provirus formation.

131 characteristically suppress transcription of proviruses formed after infection by exogenous retroviru

132 dy, we compare DNA sequences from latent SFV proviruses found in blood cells of 30 Bangladesh rhesus

133 fection may explain the high copy numbers of proviruses found in infected cells in vivo and may provi

134 ce of > 91,000 unique insertion sites of the provirus from 61 HTLV-1(+) persons and > 2100 sites from

135 me editing techniques that safely excise HIV provirus from cells, Tre, an engineered version of Cre r

136 found that AV6 reproducibly activated latent provirus from different lymphocyte-based clonal cell lin

137 human immunodeficiency virus type 1 (HIV-1) provirus from host chromosomes.

138 kinetics comparable to reconstructed induced proviruses from the same patients.

139 d an initial set of 362 potentially complete proviruses from the three main classes of ERVs, which we

140 In contrast to the proviruses from untreated cells, which were all normal,

141 HIV provirus gene-editing were confirmed by cell genomic DNA

142 in is encoded on the antisense strand of the provirus genome and entirely overlapped by the env gene

143 on led to abnormal integrations in which the provirus had one normal and one aberrant end, accompanie

144 Most of the aberrant proviruses had one normal end and one aberrant end and w

145 Strategies to target these provirus-harboring cells need to be considered for futur

146 cular, RNA from the HML-2 subgroup of HERV-K proviruses has been reported to be highly expressed at t

147 Many of these proviruses have been characterized as defective and thus

148 induced myeloid leukemia in mice, integrated proviruses have been found upstream of c-myb in three re

149 of ancestral infectious retroviruses, whose proviruses have invaded the germ-line.

150 Noninduced proviruses have unmethylated promoters and are integrate

151 In the context of the provirus, HBZ represses HTLV-1 transcription, in part, b

152 On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are express

153 One provirus, HML-2 12q24.33, in contrast, was repressed in

154 servoir by detecting replication-incompetent proviruses; however, viral outgrowth assays underestimat

155 escribe the formulation of the controversial provirus hypothesis by Temin, which ultimately was prove

156 he vast majority of the potentially complete proviruses identified in M. lucifugus were integrated in

157 o identify gRNA candidates for targeting HIV provirus in astrocytes.

158 ed infection, with low transient viremia and provirus in blood lymphocytes during acute infection.

159 th the potential to eliminate or disrupt HIV provirus in HIV reservoir cells, which may lead to a com

160 A single HERV-T provirus in hominid genomes includes an env gene (hsaHTe

161 We identified the active Bxv1 provirus in many common inbred strains and in some Japan

162 DNA looping in M1 cells and tumor cells with provirus in Mml1, Mml2, or Mml3.

163 of histone 3 at lysine 27 (H3K27) of the HIV provirus in resting cells.

164 ion in vivo is favored by orientation of the provirus in the same sense as the nearest host gene.

165 screened for their efficiencies against HIV provirus in these cells.

166 was used to analyze the distribution of both proviruses in 48 laboratory mouse strains and 46 wild-de

167 ce, modulation of the expression of specific proviruses in a given biological situation can be ascert

168 esidual viremia is genetically distinct from proviruses in activated CD4(+) T cells, monocytes, and u

169 Analysis of HIV proviruses in CD4+ lymphocytes from individuals after pr

170 ed to produce virions, compared with 1.5% of proviruses in cells treated with anti-CD3/CD28 antibodie

171 vectors, as well as that of integrated HIV-1 proviruses in latent reservoirs without significant cyto

172 The persistence of latent HIV proviruses in long-lived CD4(+) T cells despite antiretr

173 persistence of replication-competent, latent proviruses in long-lived resting T cells.

174 Thus, latent proviruses in peripheral blood mononuclear cells (PBMC)

175 that, analogously to Jurkat T cells, latent proviruses in primary CD4(+) T cells are enriched in het

176 s study, we quantified the fraction of HIV-1 proviruses in resting CD4(+) T cells from patients on su

177 of SAHA achieved clinically, only 0.079% of proviruses in resting CD4(+) T cells were reactivated to

178 ve detected the activation of HERV-K (HML-2) proviruses in the blood of patients with HIV-1 infection

179 HIV seeds reservoirs of latent proviruses in the earliest phases of infection.

180 so demonstrates that although HERV-K (HML-2) proviruses in the human genome are highly similar in ter

181 assay that detects 51 of the 89 known HML-2 proviruses in the human genome.

182 lthough the large majority (>95%) of the HIV proviruses in treated patients are defective, expanded c

183 total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with inser

184 fication of replication-competent noninduced proviruses indicates that the size of the latent reservo

185 ERVs are provirus insertions in germline cells that are inherited

186 T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA.

187 dergone clonal expansion and frequently have proviruses integrated in genes associated with regulatio

188 chronic infection, favoring establishment of proviruses integrated in transcriptionally silenced DNA:

189 e process, and the predominant SU genes from proviruses integrated in tumor DNA carried markers of ge

190 on was in the antisense orientation and from proviruses integrated within introns.

191 The provirus integration site for Moloney murine leukemia vi

192 nce remain uncertain, but integration of the provirus into the host genome represents a central event

193 cell population on ART, and insertion of HIV proviruses into certain host cellular genes has been ass

194 As is the case for all retroviruses, the provirus is inserted into the host DNA, where nucleosome

195 ected individuals harbor cells where the HIV provirus is integrated into the host's DNA but is not ac

196 xes are detected by Daxx, and the integrated provirus is rapidly chromatinized and repressed by DNA m

197 The induction of quiescent provirus is the goal of a new class of potential therape

198 ngs suggest that proliferation of cells with proviruses is a likely mechanism of HIV-1 DNA persistenc

199 ifying induced virion production from single proviruses is important for assessing the effects of HIV

200 were all normal, approximately 10-15% of the proviruses isolated after treatment with a suboptimal do

201 Interestingly, only one provirus, K103, was found to encode a functional RT amon

202 Furthermore, successfully integrated proviruses lacked detectable uracil, suggesting that onl

203 nic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus consti

204 ity of transcripts being antisense copies of proviruses located within introns.

205 proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles

206 cell line harbors a relatively low number of proviruses, making it a more promising experimental syst

207 nd molecular mechanisms that activate latent provirus may, in the presence of highly active antiretro

208 fore, bidirectional transcription across the provirus might not restrict hbz or tax expression.

209 fected 293T cells with a furin cleavage site provirus mutant, R466G/K468G, and produced the virus in

210 The system for Single-Cell Imaging of HIV-1 Provirus, named SCIP, provides the possibility to indivi

211 We found that Gag expression from integrated proviruses occurred in resting cells that lacked surface

212 In blood, we detected inducible proviruses of archival origin among highly differentiate

213 ndings suggest that the persistent defective proviruses of HIV-1 are not "silent," but rather may con

214 These patients also show persistence of proviruses of HIV-1 in circulating peripheral blood mono

215 ion of circulating cells harboring inducible proviruses of recent origin.

216 PCR was carried out for HTLV-1 provirus on buffy-coat DNAs.

217 y infected cell lines that contain two HIV-2 proviruses, one with a wild-type gag/gag-pol and the oth

218 eered into Gag from a subtype B, lab-adapted provirus or Gag from a subtype C primary isolate that wa

219 strains with Xpr1(sxv) lack the active Bxv1 provirus or other endogenous X-MLVs and may provide a us

220 ly under development aim to eradicate latent provirus, or prevent viral replication, progression to A

221 assumed to be stable and to contain one HIV provirus per cell.

222 fails to cure HIV-1 infection because latent proviruses persist in resting CD4(+) T cells.

223 -1) but does not cure the infection, because proviruses persist in stable latent reservoirs.

224 oviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with th

225 r, we found that the host mice contained two proviruses, PreXMRV-1 and PreXMRV-2, which share 99.92%

226 IV-1 DNA levels, suggesting that reactivated proviruses proliferate.

227 ed on ART) revealed that an average of 7% of proviruses (range: 2-18%) expressed HIV RNA.

228 eeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated.

229 Transcriptional latency of integrated HIV-1 provirus represents a major obstacle to curing HIV.

230 y dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ES

231 c1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Tri

232 xistence of latent but replication-competent proviruses residing primarily in a very small population

233 sion of L9 in cells expressing the MMTV(C3H) provirus resulted in specific, robust accumulation of Ga

234 K111 proviruses show significant sequence variations in each

235 vates expression of 26 unique HERV-K (HML-2) proviruses, silences 12, and does not significantly alte

236 /Atf7ip) are key determinants that establish provirus silencing.

237 ed on Tat-treated PBLs of seven donors using provirus-specific primers and corroborated the results w

238 , while modern humans have at least 100 K111 proviruses spread across the centromeres of 15 chromosom

239 ajor ERV classes include recently integrated proviruses, suggesting that a wide diversity of retrovir

240 y expanded Th1 cells containing intact HIV-1 proviruses, suggesting that this polarized subset contri

241 mine whether the proliferation of cells with provirus sustain HIV-1 persistence in spite of effective

242 nologically silent but replication-competent proviruses - termed the latent reservoir.

243 tivates expression of a novel HERV-K (HML-2) provirus, termed K111, present in multiple copies in the

244 haracteristics of the latent, integrated HIV provirus that persists during treatment are associated w

245 wl produce piRNAs targeting ALV from one ALV provirus that was known to render its host ALV resistant

246 nus) and elk (Cervus canadensis) DNA contain proviruses that are closely related to mule deer CrERVga

247 type K (HERV-K) HML-2 (HK2) family contains proviruses that are the most recent entrants into the hu

248 nknown, however, is the proportion of latent proviruses that can be transcriptionally reactivated by

249 human immunodeficiency virus type 1 (HIV-1) proviruses that express unspliced viral RNA in vivo or a

250 o express HIV RNA at levels similar to those proviruses that had no obvious defects.

251 onded poorly to external stimuli carried HIV proviruses that were enriched in H3K27me3 and relatively

252 V DNA content, which also includes defective proviruses that would not be able to replicate and initi

253 Polydnaviruses are vertically transmitted as proviruses through the germ line of wasps but also funct

254 d immediately after the activation of latent proviruses through the TCR.

255 ession originating from 15 HML-2 full-length proviruses, through four modes of transcription.

256 rochromatin structures present on the latent provirus to active euchromatin structures containing ace

257 ucted by engineering a CCR5-tropic subtype A provirus to express SIV vif, which counters the macaque

258 We found 15 proviruses to be significantly expressed through four di

259 Knockdown of EZH2 also sensitized latent proviruses to external stimuli, such as T-cell receptor

260 ion, and slowed the reversion of reactivated proviruses to latency.

261 stances of long terminal repeat (LTR)-driven provirus transcription but no evidence to suggest that t

262 Our studies reveal that CD28 regulates HIV-1 provirus transcription through a complex interplay of po

263 d a relatively large reduction in integrated proviruses upon NUP153 knockdown.

264 Lastly, direct detection of HIV-1 proviruses using fluorescence in situ hybridization conf

265 es transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with ta

266 d by the emergence or expansion of X4-tropic provirus variants.

267 tion after T-cell activation from individual proviruses varies by 10,000-fold to 100,000-fold.

268 onesia were positive, yielding an endogenous provirus very closely related to a strain of GALV.

269 ients, the documented expansion of X4-tropic provirus was based on the outgrowth of single viral vari

270 One CrERVgamma provirus was detected in all mule deer sampled but was a

271 Similarly, reactivation of latent provirus was facilitated in the absence of CYLD.

272 nes was significantly more frequent when the provirus was integrated near host genes in specific gene

273 A CrERVgamma provirus was sequenced and contained intact open reading

274 Integration of the uracilated proviruses was restored using an isogenic cell line that

275 ong terminal repeat (LTR) from Vpr-deficient proviruses was significantly reduced.

276 of an integrated form of retroviral DNA (the provirus) was first proposed by Howard Temin in 1964.

277 and reconstructed patient-derived defective proviruses, we show that defective proviruses can be tra

278 RNAP II pause sites on the HIV provirus were mapped to high resolution by ChIP with hig

279 ose host genes harboring a latent integrated provirus were transcriptionally active, mostly at high l

280 Cells containing the intact provirus were widely distributed and significantly enric

281 High-producing proviruses were associated with increases in cell-associ

282 The chromosomal loci of both proviruses were determined in the mouse genome, and inte

283 RNA sequences from novel HERV-K (HML-2) proviruses were discovered, including K111, which is spe

284 In addition, we found that HML-2 proviruses were expressed in multiple blood cell types f

285 Defective proviruses were found to express HIV RNA at levels simil

286 rved in prokaryotic genomes outside detected proviruses were identified for two-thirds of the 57 taxa

287 e on ART, a greater proportion of persisting proviruses were in proliferating cells.

288 ts EZH2, led to the reactivation of silenced proviruses, whereas chaetocin and BIX01294 showed only m

289 and long-read sequencing to study the HIV-1 provirus, which is only 9700 bp in length, but encodes n

290 ly undetected, large group of HERV-K (HML-2) proviruses, which are descendants of the ancestral K111

291 rsing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective an

292 Additionally, the expression of defective proviruses will need to be considered in the measurement

293 DNA was screened for XMRV provirus with two sensitive, published PCR assays target

294 Proviruses with defective major splice donors (MSDs) can

295 We observed proviruses with single APOBEC3G-mediated mutations (in t

296 romatin organization allows distally located provirus, with its own enhancer elements, to access the

297 dual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus

298 lasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4(+)

299 eservoir have focused on reactivating latent proviruses without inducing global T cell activation.

300 compounds that selectively reactivate latent proviruses without inducing polyclonal T cell activation