ライフサイエンスコーパス: provirus

1 cell clone harboring a replication-competent provirus.

2 to genotoxic integrations of the therapeutic provirus.

3 us at all sites reported to contain a HERV-K provirus.

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

5 els similar to those in cells containing one provirus.

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

7 omoter-driven transcription of an integrated provirus.

8 genetic structure of the gag region in each provirus.

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

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

11 require prior establishment of an integrated provirus.

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

13 intermediates in cells expressing the HIV-1 provirus.

14 03(-) cells but transcribed less HIV RNA per provirus.

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

16 with recognizable hallmarks of an integrated provirus.

17 that harbor latent but replication-competent provirus.

18 CD4+ T cells harboring replication-competent provirus.

19 s with any combination of polymorphic HERV-K provirus.

20 t separately quantifies intact and defective proviruses.

21 moving flanking host regions from integrated proviruses.

22 la-specific integrations, including 31 2-LTR proviruses.

23 eting cells with specific types of defective proviruses.

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

25 of transcription from an extensive range of proviruses.

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

27 termined by the number of genetically intact proviruses.

28 o successful therapy to eradicate integrated proviruses.

29 eated early failed to detect sequence-intact proviruses.

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

31 y expanded cells carry replication-competent proviruses.

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

33 he proportions of various types of defective proviruses.

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

35 and nonhuman primate cells expressing HIV-1 proviruses.

36 ies exist to selectively activate latent HIV proviruses.

37 packaging and virus titer in the context of proviruses.

38 cantly alter the expression of the remaining proviruses.

39 from recombination events involving multiple proviruses.

40 ted in archaeal and bacterial viruses and in proviruses.

41 with wild-type and drug-resistant defective proviruses.

42 a long-lived latent reservoir of integrated proviruses.

43 re and maintain a stable number of total HIV proviruses.

44 mans, and the only group with human-specific proviruses.

45 oir of transcriptionally inactive integrated proviruses.

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

47 one round of activation does not induce all proviruses(7).

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

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

50 5, X4, and R5/X4), six primary isolates, and provirus-activated ACH-2 cells examined.

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

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

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

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

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

56 asurements assess various aspects of the HIV provirus and its functionality and produce divergent res

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

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

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

60 ow that naive CD4(+) T cells harbored intact provirus and were a major contributor to blood and lymph

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

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 city' metric, genes associated with archaeal proviruses and genes linked to Argonaute genes in haloba

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

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

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

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

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

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

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

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

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

77 e assays is unclear, as the vast majority of proviruses are defective(7-9).

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

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

80 ics of cells that carry intact and defective proviruses are different in vitro and in vivo.

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

82 However, HML-2 proviruses are found throughout the catarrhine primates,

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

84 e recently demonstrated that these defective proviruses are not silent, are capable of transcribing n

85 However, intact proviruses are present at substantially higher frequenci

86 that cells harboring genetically intact HIV proviruses are rare in children exhibiting long-term sup

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

88 The identified proviruses are related to tailed viruses of the order Ca

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

90 As these defective proviruses are unable to encode intact and replication-c

91 part because population prevalence of HERV-K provirus at each polymorphic site is lacking and it is c

92 Concordantly, total proviruses at later time points or observed in clones we

93 ation-specific sequence variation for HERV-K proviruses at several loci.

94 esponses, had a smaller proportion of intact proviruses but a distribution of defective provirus type

95 We observed slow decay of intact proviruses but no changes in the proportions of various

96 ot originate directly from individual latent proviruses but rather from recombination events involvin

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

98 ted de novo virus production from integrated proviruses by blocking the accumulation of HIV RNAs that

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

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

101 efective proviruses greatly outnumber intact proviruses (by >12.5 fold).

102 Rare, intact proviruses can be detected in children who initiate ART

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

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

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

106 distinction is important because only intact proviruses cause viral rebound on ART interruption.

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

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

109 ses the turnover of intrinsically long-lived provirus-containing CD4(+) T cells.

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

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

112 We showed that rare, genetically intact proviruses could be detected in children who initiated A

113 epresent sequences that closely resemble the proviruses created from exogenous retroviral infection.

114 Gaining a better understanding of why intact proviruses decay faster in vitro might help the field id

115 o distinguish and separately quantify intact proviruses, defined by a lack of overt fatal defects suc

116 ncies (median, 54/10(6) CD4(+) T cells) than proviruses detected by the quantitative viral outgrowth

117 Greater than 95% of these proviruses detected in circulating peripheral blood mono

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

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

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

121 " cells, Jurkat cells harboring a latent HIV provirus encoding an enhanced green fluorescent protein

122 nces, increase relatively to other defective proviruses, especially among clones.

123 2 clones from 1 donor that carried identical proviruses except for nonoverlapping deletions, from whi

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

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

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

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

128 pharmacological ap-proach aims to reactivate provirus expression in the presence of antiretroviral th

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

130 Many maintain intact open reading frames and provirus expression together with HML2 particle formatio

131 the reversal of post-integrated latent HIV-1 proviruses for purging of reservoir cells.

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

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

134 or restricting HIV-1 infection by preventing provirus formation.

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

136 the full-length infectious TG35-2-phenotypic provirus from a naturally FeLV-infected cat, from which

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

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

139 Integration sites for infectious proviruses from those 4 donors were mapped to the intron

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

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

142 direct quantitative evidence that defective proviruses greatly outnumber intact proviruses (by >12.5

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

144 One identified provirus has full-length ORFs for all genes, and thus co

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

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

147 Many of these proviruses have identical LTRs, and are insertionally po

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

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

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

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

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

153 hese iMGE group into five major classes: (i) proviruses, (ii) casposons, (iii) insertion sequence-lik

154 The single report of an HIV provirus in a case of AIDS-associated B-cell lymphoma wi

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

156 Induced provirus in CD32hiCD4+ T cells replicated to substantial

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

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

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

160 class I HDACs implicated in maintaining HIV provirus in the latent state.

161 AIDS-associated B-cell lymphoma with an HIV provirus in the same part of STAT3 also has implications

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

163 hromosomal positions of intact and defective proviruses in 3 HIV-1-infected individuals undergoing lo

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

165 sequencing to evaluate intact and defective proviruses in blood and lymph node CD4 T cells enriched

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

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

168 nded clones was similar to that of defective proviruses in clones.

169 The proportion of intact proviruses in expanded clones was similar to that of def

170 e failed to reveal any replication-competent proviruses in humans.

171 HIV-1 persists as transcriptionally inactive proviruses in infected cells.

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 fected cells harboring translation-competent proviruses in longitudinal samples from eight individual

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

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

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

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

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

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

181 tion of our work is that the decay of intact proviruses in vitro is extremely rapid, perhaps as a res

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

183 using on the genetic integrity of individual proviruses independent of transcriptional status.

184 ERVs are provirus insertions in germline cells that are inherited

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

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

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

188 sident T cells, and permanent integration of provirus into neural cells such as microglia and astrocy

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

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

191 This hidden provirus is protected from antiviral drugs until it even

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

193 roliferation of CD4+ T cells harboring HIV-1 proviruses is a major contributor to viral persistence i

194 alable approach for quantifying intact HIV-1 proviruses is critical for basic research and clinical t

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

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

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

198 ation of infected cells or greatly alter the provirus landscape in people on ART.

199 otoxic T lymphocyte (CTL) pressure shape the provirus landscape, we performed an intact proviral DNA

200 of human endogenous retroviruses, with many proviruses less than one million years old.

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

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

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

204 e, the viral proteins coded in the defective proviruses may form extracellular virus-like particles a

205 A transcripts expressed from these defective proviruses may trigger an element of innate immunity.

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

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

208 In a fraction of HERV-K loci (Type 2 proviruses), nuclear export of the unspliced HERV-K mRNA

209 t have more escaped CTL epitopes than intact proviruses observed as singlets.

210 Intact proviruses observed in clones did not have more escaped

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 integrated into the host genome to form the provirus or act as a target of the DNA damage response a

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

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

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

221 de insight on the mechanisms by which intact proviruses persist and inform ongoing cure efforts.

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

223 HIV-1 proviruses persist in the CD4(+) T cells of HIV-infected

224 e southern population (P < 0.0001), and many provirus-positive southern animals failed to express any

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

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 ter cell line, which quantifies specific HIV provirus reactivation (LTR promoter) relative to nonspec

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

230 e antiviral treatment, the majority of these proviruses remain transcriptionally silent, but mechanis

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

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

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

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

235 say (IPDA) and obtained 661 near-full-length provirus sequences from 8 individuals with suppressed vi

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

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

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

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

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

241 an expanded T cell clone carrying an intact provirus that matched a variant previously detected by v

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

243 ived from the lymph node appeared to contain provirus that was genetically identical to plasma-derive

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

245 s have implications for targeting the intact proviruses that are a barrier to curing HIV infection.

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

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

248 We find intact and defective proviruses that contain genetic elements favoring effici

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 mediated hypermutation, from the majority of proviruses that have such defects.

252 Moreover, proviruses that lack these genetic elements, yet contain

253 cure strategies is complicated by defective proviruses that persist in ART-treated patients but are

254 s, we are able to demonstrate that defective proviruses that persist in HIV-infected individuals duri

255 therapy (ART) during acute infection, 2% of proviruses that persist on ART are genetically intact by

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

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

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

259 voir), with an estimated 1:2 ratio of intact provirus to total viral DNA.

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

261 nriched for replication-competent and intact provirus, transcribed HIV, and displayed clonal expansio

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

263 t proviruses but a distribution of defective provirus types and escaped or unrecognized epitopes simi

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

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

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

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

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

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

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

271 he frequency of naive cells harboring intact provirus was lower than in memory cells, the high abunda

272 The frequency of intact proviruses was lower (P < 0.05) than that reported for H

273 The decay of integrated intact proviruses was rapid and similar in both quiescent and a

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

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

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

277 alence of individual and co-occurring HERV-K proviruses; we provide a visualization tool to easily de

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

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

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

281 No intact proviruses were detected in four children who initiated

282 ruses with defective sequences, intact HIV-1 proviruses were enriched for non-genic chromosomal posit

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

284 expanded clones of T cells bearing identical proviruses were found in blood and lymph node.

285 cells containing defective or intact latent proviruses were found in seven of eight individuals stud

286 Instead, latent proviruses were found to contribute to the rebound compa

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

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

289 In addition, intact HIV-1 proviruses were preferentially integrated in either rela

290 We observed that the frequencies of intact proviruses were the same in blood and lymph node.

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

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

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

294 Proviruses with defective major splice donors (MSDs) can

295 We observed that in comparison to proviruses with defective sequences, intact HIV-1 provir

296 studies strongly suggest selection of intact proviruses with features of deeper viral latency during

297 Proviruses with identical sequences, identical integrati

298 to determine the clonality and structure of proviruses within expanded clones, including those with

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

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