ライフサイエンスコーパス: BKV

1 BKV and JCV were commonly detected in the urine of lung

2 BKV and mouse polyomavirus were used to infect human and

3 BKV DNA surveillance was performed at 1, 3, 6, 12, and 2

4 BKV genotype-specific NAb titers may be a meaningful pre

5 BKV infection of primary human TEC did not induce an ant

6 BKV infection progresses to BKV nephritis (BKVN) in appr

7 BKV infection was associated with poorer survival.

8 BKV PCR testing of donor urine may be useful in identify

9 BKV reactivation in immunosuppressed patients or renal t

10 BKV serostatus can be used to risk stratify patients for

11 BKV specifically evades innate immunity in TEC and is no

12 BKV subtype III is rarely identified and has not previou

13 BKV subtype IV had a higher prevalence in recipients wit

14 BKV subtype IV may be one of the viral determinants.

15 BKV viremia was observed in 20% of the desensitized and

16 BKV VP1 sequencing revealed identical virus between dono

17 BKV was monitored every 2 months in the urine or blood.

18 BKV whole genomes were amplified using long-range PCR wi

19 Prototype 1 (BKV Dun) could be reliably detected at concentrations as

20 th a minority before (7.8%) or after (40.1%) BKV clearance.

21 uses, including simian vacuolating virus 40, BKV, and JCV.

22 reviously reported cutoff value of 6.5x10(5) BKV viral capsid protein 1 (VP-1) mRNA/ng RNA in urinary

23 aried significantly among viruses: JCV, 64%; BKV, 48%; and SV40, 14%.

24 ignaling pathways that target them) activate BKV replication and contribute to the consequent patholo

25 f 37.0 (P=0.1216) after resolution of active BKV infection.

26 ation of fluoroquinolone prophylaxis against BKV infection remain unknown.

27 appear to be markers for protection against BKV infection (OR: 0.29, 95% CI: 0.1-0.83, P=0.01 for rs

28 ne prophylaxis directed specifically against BKV has not been formally tested against a control group

29 However, consistent detection of all BKV variants was possible only at concentrations of 10,0

30 P-10, cytotoxic perforin and granzyme B, and BKV VP1 mRNA were not different (P>0.05) between HIV-inf

31 tigated the urine virome profile of BKV+ and BKV- kidney transplant recipients.

32 ntitative viral replication of CMV, EBV, and BKV in oral washes, urine, and whole blood pretransplant

33 and 65.5% for the detection of CMV, EBV, and BKV, respectively.

34 as MLL4) gene loci in liver cancer, HPV and BKV in bladder cancer, and EBV in non-Hodgkin's lymphoma

35 n a state of increased immunosuppression and BKV infection, especially in patients with higher MMF ex

36 e the structure-based design of dual JCV and BKV ATP-competitive inhibitors.

37 , the susceptibility of CRC cells to JCV and BKV was examined using a long-term cultivation approach

38 tions caused by human polyomaviruses JCV and BKV.

39 a risk factor for subsequent BKV viremia and BKV-associated nephropathy.

40 Any BKV infection developed in 25 of 41, 22 of 42, 17 of 41,

41 ], and D-R- [n=68]), 89 of 192 developed any BKV infection and 62 of 89 developed BK insignificant vi

42 ic regression model showed lower risk of any BKV infection in African American recipient race (OR, 0.

43 The outcomes studied were development of any BKV infection, viremia, and significant viremia (>/=10,0

44 As BKV-specific treatments are limited, immunologic-based t

45 ia and 25 had significant viremia defined as BKV DNA more than 10,000 copies/mL of plasma.

46 entify BKV variants across the genome and at BKV-specific HLA-A2-, HLA-B0702-, and HLA-B08-restricted

47 f mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings.

48 KV nephropathy group, urine and blood became BKV positive earlier than in the group with viruria and

49 these results support an association between BKV and urothelial carcinogenesis among kidney transplan

50 Here we investigated the interplay between BKV and TEC in more detail.

51 Reactivation of polyomavirus BK (BKV) after renal transplantation can lead to allograft d

52 Knowledge of polyomavirus BK (BKV) genomic diversity has greatly expanded.

53 Polyomavirus BK (BKV) infection can cause nephropathy in the allograft ki

54 Polyomavirus BK (BKV) infection characterized by viruria alone is conside

55 ation increases the risk of polyomavirus BK (BKV) viremia.

56 marker that allows patient stratification by BKV disease risk before and after transplant.

57 of renal function and prevention of clinical BKV nephritis and graft loss.

58 Comparing BKV subtypes of donor and recipient before with the subt

59 Human IVIG preparations contain BKV neutralizing antibodies.

60 In contrast, BKV infection of leukocytes did elicit an antiviral resp

61 of caveolin-1, prevented caveolar-dependent BKV internalization and repressed BKV infection of HRPTE

62 Donor-derived BKV transmission is an important mode of infection.

63 Together with reports describing BKV detection in tumor tissues, these results support an

64 eceased donors, 8.1% (17/208) had detectable BKV DNA in urine prior to organ procurement.

65 y two patients (8.7%) with UC had detectable BKV.

66 A surveillance strategy for detecting BKV reactivation based on urine cytology is cost-effecti

67 A total of 94 developed BKV infection (any degree of BK viruria or viremia) wher

68 er proportion of African Americans developed BKV infection, 14 of 61 (23%), as opposed to whites, 67

69 arison of Altona with a laboratory-developed BKV NAAT assay in IU/ml versus copies/ml using Passing-B

70 cating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence int

71 tional unit (IU) using the Exact Diagnostics BKV verification panel, a secondary standard traceable t

72 The finding implies that different BKV genotypes have different cellular tropisms and patho

73 fter transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (

74 orter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera

75 Donor BKV replication occurred in 17%, mostly in the urine and

76 Though donor BKV IgG titers were higher in recipients who developed B

77 Early BKV positivity of urine and blood indicates later BKV ne

78 donor transmission in 95% of cases of early BKV replication.

79 ellular immune response to peptides encoding BKV large T antigen.

80 Decreased renal function may favor BKV infection.

81 For BKV prototypes with 2 or more mismatches (representing g

82 l and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7),

83 ecipients from January 2007 to June 2011 for BKV and/or CMV viremia.

84 least once, including 38 patients (42%) for BKV, 25 patients (28%) for JCV, and six patients (7%) fo

85 as a previously unrecognized risk factor for BKV reactivation after renal transplantation.

86 mia or viruria, analysis of risk factors for BKV nephritis as an endpoint could lead to erroneous fin

87 te globulin are independent risk factors for BKV replication in renal allograft recipients treated wi

88 ent of BK viremia, specific risk factors for BKV-related complications in the transplant setting rema

89 /L (AHR, 3.6; P=0.001) were risk factors for BKV.

90 Urinary viral loads for BKV (10 copies/mL) and JCV (10 copies/mL) were higher th

91 body (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers

92 in the presence of viruria but negative for BKV stains were designated as putative T-cell-mediated a

93 fer certain protection or predisposition for BKV infection.

94 endent increase in viral DNA replication for BKV, MCV and HPyV7.

95 hese data indicate that NFAT is required for BKV infection and is involved in a complex regulatory ne

96 useful in identifying recipients at risk for BKV complications.

97 ciated with a significantly reduced risk for BKV infection (OR: 0.43, 95% CI: 0.25-0.73, P=0.001).

98 nt recipients may identify those at risk for BKV-associated nephropathy.

99 The 1st WHO International Standard for BKV (primary standard) was introduced in 2016 as a commo

100 More frequent surveillance for BKV viremia and an early, aggressive treatment strategy

101 Surveillance for BKV viremia was done at 1, 2, 3, 6, 9, and 12 months pos

102 e feasible by measurement of transcripts for BKV viral capsid protein 1 (VP-1), GB, and PI-9 in urine

103 Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete

104 is shows a trend toward greater freedom from BKV infection in African Americans as opposed to other r

105 After repeat transplant, 11 (35%) had BKV replication in urine and plasma with two patients ex

106 A was undetectable at 24 months and none had BKV replication.

107 While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of su

108 aceable to the primary standard to harmonize BKV NAAT results, we anticipate improved interassay comp

109 Here, BKV viremia in HLA-sensitized patients after desensitiza

110 t strategy are essential for preventing high BKV viral loads in this patient population.

111 However, BKV infection did not affect dsDNA-induced gene expressi

112 gy and bioinformatics pipeline that identify BKV variants across the genome and at BKV-specific HLA-A

113 e the whole-genome sequence of a subtype III BKV from a pediatric kidney transplant patient with poly

114 amine the role of antimicrobial defensins in BKV infection of Vero cells.

115 ever, there was no significant difference in BKV-associated nephropathy or graft loss in the two grou

116 (NFAT) plays an important regulatory role in BKV infection.

117 Renal function was worse in BKV-nephropathy compared with BKV-negative patients begi

118 ct dsDNA-induced gene expression, indicating BKV did not modulate the antiviral response.

119 ors (D)-recipient (R) pairs using infectious BKV neutralization assays with representatives from the

120 Fluoroquinolones inhibit BKV replication in vitro, and small studies suggest in v

121 P1) and human alpha-defensin 5 (HD5) inhibit BKV infection by targeting an early event in the viral l

122 ion of certain misfolded proteins, inhibited BKV infection.

123 competition with templates containing intact BKV NCCRs.

124 present the outcomes from an early intensive BKV surveillance program using decoy cell detection for

125 ntially oncogenic viruses such as SV40, JCV, BKV and EBV in patient-derived colorectal carcinoma (CRC

126 ue were analyzed for sequences of SV40, JVC, BKV and EBV using endpoint PCR.

127 It was found that currently known BKV subtypes and subgroups can no longer be reliably det

128 viridae: Aichi virus (AV), bovine kobuvirus (BKV), canine kobuvirus (CKoV), mouse kobuvirus (MKoV), s

129 d interfered with internalization of labeled BKV particles.

130 ositivity of urine and blood indicates later BKV nephropathy.

131 different standards to prospectively measure BKV titers in 251 urine specimens submitted to our clini

132 tive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed p

133 from 14 copies/ml (HHV-6) to 191 copies/ml (BKV), and the lower limit of quantitation ranged from 44

134 gan transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing post

135 e in antibiotic prophylaxis practice from no BKV prophylaxis (Group 1, n=106, July-December 2009) to

136 were evaluated in three eras: (i) Era-I: No BKV PCR performed (n = 36), (ii) Era-II: PCR performed f

137 demonstrate nanomolar inhibition (EC(50)) of BKV infection and suggest that the peptide acts early in

138 significantly associated with the absence of BKV replication after repeat transplantation.

139 The activation of BKV replication following kidney transplantation, leadin

140 There was an association of BKV viremia with desensitization and lymphocyte inductio

141 nce and regulatory micro (mi)RNA clusters of BKV, JCV and SV40.

142 Coincubation of BKV but not mouse polyomavirus with clinically relevant

143 source and factors influencing the course of BKV infection.

144 The sensitivity of detection of BKV in the PCR assay was a function of the viral genotyp

145 Detection of BKV infection very early (ie, 5 days) after transplantat

146 41%, respectively, from time of diagnosis of BKV infection to complete resolution of viremia.

147 mbers interacted with the helicase domain of BKV Tag in pulldown assays, suggesting that NFI helps re

148 ore and after transplantation; genotyping of BKV subtypes was performed.

149 alibrator for improving the harmonization of BKV nucleic acid amplification testing (NAAT) and enabli

150 The implications of BKV DNA sequence variation for the performance of molecu

151 The incidence of BKV infection in the total population was 163 of 609 (26

152 mab is associated with a higher incidence of BKV viremia with high viral copies and was the major pre

153 proteins VP2/3 that is a potent inhibitor of BKV infection with no observable cellular toxicity.

154 applicable thresholds for the management of BKV infection in transplantation.

155 luate the risk factors for the occurrence of BKV infections using BK viruria and viremia as endpoints

156 ucted to determine incidence and outcomes of BKV infection.

157 Both the percentage of BKV infected cells and the large T-antigen expression we

158 viral copies and was the major predictor of BKV viremia in the multivariable model.

159 ansplantation and tested for the presence of BKV by polymerase chain reaction.

160 ents were tested by qPCR for the presence of BKV DNA before and after transplantation; genotyping of

161 The prevalence of BKV replication increased over time and was highest at 6

162 we investigated the urine virome profile of BKV+ and BKV- kidney transplant recipients.

163 ecipients is associated with a lower rate of BKV infection at 3 months but not at 12 months.

164 We hypothesize that the rate of BKV infection can be curbed by competitively preventing

165 2, n=130, January-June 2010) on the rate of BKV infection during the first 12 months after kidney tr

166 were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malign

167 The replication of BKV DNA in cell cultures is regulated by the viral nonco

168 alpha or dsDNA did not hamper replication of BKV, whereas influenza and herpes simplex virus 1 replic

169 tatus may be useful in assessing the risk of BKV infection in kidney transplant recipients.

170 so investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative

171 was to characterize the course and source of BKV in kidney transplant recipients.

172 Using the Dunlop strain of BKV, we found that nuclear factor of activated T cells (

173 oads were significantly higher than those of BKV in both patient groups (P< .0001).

174 To assess the value of BKV genotype-specific neutralizing antibody (NAb) titers

175 sialogangliosides, which bind to the VP1 of BKV, also associate with our BKV template.

176 as found in the viral coat protein, VP1, of BKV.

177 Based on BKV-specific IgG enzyme immunoassay >/=8 units, subjects

178 Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BK

179 ype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppr

180 d to the VP1 of BKV, also associate with our BKV template.

181 ing and deceased kidney donors and performed BKV polymerase chain reaction (PCR) and immunoglobulin G

182 on for transplant recipients with persistent BKV infection.

183 At time of diagnosis, mean plasma BKV DNA (copies/mL) was 460,409 (range 10,205-1,920,691)

184 The mean plasma BKV DNA declined by 98% (range, 76%-100%) at 1 year afte

185 stein-Barr virus (EBV), and BK polyomavirus (BKV) at transplant was a risk factor for posttransplant

186 BK polyomavirus (BKV) causes significant urinary tract pathogenesis in im

187 BK polyomavirus (BKV) establishes persistent, low-level, and asymptomatic

188 kidney transplant patients, BK polyomavirus (BKV) has been shown to induce nephropathy (BKVN), decrea

189 eries describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recip

190 The pathogenesis of BK polyomavirus (BKV) infection and associated nephropathy in renal trans

191 BK polyomavirus (BKV) infection remains a significant cause of nephropath

192 BK polyomavirus (BKV) is an emerging pathogen in immunocompromised indivi

193 a peptide derived from the BK polyomavirus (BKV) minor structural proteins VP2/3 that is a potent in

194 BK polyomavirus (BKV)-associated nephropathy is a threat to kidney allogr

195 quency of urinary shedding of polyomaviruses BKV and JCV and their relationship to creatinine clearan

196 reduce the risk of developing posttransplant BKV disease.

197 ican race had a lower risk of posttransplant BKV infection compared with whites, independent of other

198 o evaluate various aspects of posttransplant BKV infection.

199 recipient serostatus to posttransplantation BKV infection.

200 ients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United State

201 retrospectively determined the pretransplant BKV neutralizing serostatus of 116 donors (D)-recipient

202 Pretransplantation BKV serostatus was available for 192 adult and 11 pediat

203 tralizing antibodies can moderate or prevent BKV disease.

204 omes, acute rejection rate, HIV progression, BKV replication, infections, and urinary cell mRNA profi

205 end toward higher incidence of biopsy-proven BKV nephropathy in Group 1 (4.7% vs. 0.8%, P=0.057).

206 HCT and kidney recipients with quantifiable BKV DNAemia underwent whole-genome sequencing.

207 This included 7453 quantitative BKV polymerase chain reaction and 15,496 quantitative CM

208 establishing broadly applicable quantitative BKV DNA load cutoffs for clinical practice.

209 Here, we evaluated the Altona RealStar BKV assay (Altona) and calibrated the results to the int

210 BKV replication is associated with recipient BKV viremia in kidney transplants.

211 ion, either individually or in toto, reduces BKV DNA replication when placed in competition with temp

212 red T-cell epitopes similar to the reference BKV strain that was matched for the BKV genotype.

213 -dependent BKV internalization and repressed BKV infection of HRPTEC.

214 Clinically significant BKV reactivation occurs early after transplantation and

215 .82; P=0.016) and higher risk of significant BKV infection with occurrence of acute rejection (OR, 3.

216 ies of NFI: the NFIC/CTF1 isotype stimulates BKV template replication in vitro at low concentrations

217 underwent biopsy presented with subclinical BKV nephritis.

218 s identified as a risk factor for subsequent BKV viremia and BKV-associated nephropathy.

219 nts demonstrated a higher rate of subsequent BKV viremia than patients with antecedent CMV viremia (P

220 d large T-antigen expression which suggested BKV infection by Western blots was assessed in the absen

221 Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinc

222 s that potently cross-neutralized all tested BKV genotypes.

223 The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct sero

224 Our results demonstrate that BKV infection in RPTE cells involves an acidic environme

225 These results indicate that BKV early entry and disassembly are highly regulated pro

226 These findings suggest that BKV and JCV display different patterns of reactivation a

227 idney transplant recipients, suggesting that BKV could contribute to the development of these cancers

228 ly available VP-1 sequences encompassing the BKV genomic region targeted by an in-house quantitative

229 eference BKV strain that was matched for the BKV genotype.

230 In the BKV nephropathy group, urine and blood became BKV positi

231 While the BK virus was predominant in the BKV+ group, it was also found in the BKV- group patients

232 in the BKV+ group, it was also found in the BKV- group patients.

233 Analysis of the BKV subtypes showed that nucleotide polymorphisms were d

234 tingly, we detected multiple subtypes of the BKV, JCV and TTV.

235 These data demonstrate that the BKV template mimics the host cell binding observed for t

236 axis (Group 1, n=106, July-December 2009) to BKV prophylaxis with ciprofloxacin 250 mg twice daily fo

237 show a novel mechanism whereby HD5 binds to BKV leading to aggregation of virion particles preventin

238 No grafts were lost due to BKV during the study period.

239 w that proteasome function is also linked to BKV infection and capsid rearrangement.

240 d inhibits infection with similar potency to BKV in a model cell line.

241 BKV infection progresses to BKV nephritis (BKVN) in approximately 8% of transplants

242 nificantly associated with susceptibility to BKV infection (OR: 2.9, 95% CI: 1.29-6.44, P=0.007) whil

243 P=0.02), and a significantly shorter time to BKV viremia (P=0.01) in kidney recipients.

244 cells (TEC) show a limited response towards BKV infection.

245 Donor urinary BKV replication is associated with recipient BKV viremia

246 Pretransplant urinary BKV shedding of donor and recipient is a risk for posttr

247 Pretransplant urinary BKV shedding of donor or recipient was a significant ris

248 ciated with posttransplant recipient urinary BKV replication in recipients, it was associated with BK

249 In conclusion, variant BKV strains lower the sensitivity of detection and may h

250 only two disease-causing members (BK virus (BKV) and JC virus (JCV)) identified.

251 riability in the quantification of BK virus (BKV) DNA precludes establishing broadly applicable thres

252 Quantitative BK virus (BKV) DNA surveillance in plasma/urine was performed at 1

253 ransplant recipients, particularly BK virus (BKV) in kidney transplant patients.

254 the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC)

255 imited data on the epidemiology of BK virus (BKV) infection after alemtuzumab induction.

256 BK virus (BKV) infection causing end-organ disease remains a formi

257 BK virus (BKV) infection of kidney transplant patients is an incre

258 widely recognized risk factor for BK virus (BKV) infection, particularly with the combination of tac

259 Cytomegalovirus (CMV) and BK virus (BKV) infections can cause significant morbidity after ki

260 The human polyomavirus BK virus (BKV) is a common virus for which 80 to 90% of the adult

261 BK virus (BKV) is a polyomavirus that establishes a lifelong persi

262 BK virus (BKV) is a significant cause of nephropathy in kidney tra

263 Because the occurrence of BK virus (BKV) nephritis is far less frequent than BK viremia or v

264 BK virus (BKV) nephropathy remains the main cause of renal graft l

265 Identification of risk factors for BK virus (BKV) replication may improve transplant outcome.

266 case of the human polyomaviruses, BK virus (BKV) replication occurs in the tubular epithelial cells

267 s (CMV), Epstein-Barr virus (EBV), BK virus (BKV), adenovirus (ADV), and human herpesvirus 6 (HHV6) w

268 irus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).

269 Samples were analyzed for BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) by conv

270 PV), Epstein-Barr virus (EBV), and BK Virus (BKV), suggesting the involvement of these viruses in ear

271 BK virus (BKV)-associated nephropathy is the second leading cause

272 relationship of pretransplantation BK virus (BKV)-specific donor and recipient serostatus to posttran

273 MV), Epstein-Barr virus (EBV), and BK virus (BKV).

274 rr virus (EBV), and 64 (34.6%) for BK virus (BKV).

275 quent detection of polyomaviruses (BK virus [BKV] or simian virus 40 [SV40]) in 46% of stool samples

276 (dsDNA) viruses (adenovirus [ADV], BK virus [BKV], cytomegalovirus [CMV], Epstein-Barr virus [EBV], h

277 HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously w

278 than kidney recipients (71% vs 38%), whereas BKV was shed more often by kidney than liver patients (6

279 KoV also contain these four domains, whereas BKV, SKV, and TV2/TV3 5' UTRs contain domains that are r

280 In particular, we questioned whether BKV suppresses and/or evades antiviral responses.

281 It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV

282 core origin and flanking sequences, to which BKV T antigen (Tag), cellular proteins, and small regula

283 re positive for human polyomaviruses: 9 with BKV, 9 with JC virus (JCV), 1 with SV40, and 1 with both

284 Risk factors associated with BKV infection in univariate analyses were retransplantat

285 IFN-gamma polymorphisms are associated with BKV infection.

286 ore transplant significantly associated with BKV replication after transplant (HR, 1.88; 95% CI, 1.06

287 cation in recipients, it was associated with BKV viremia (P=0.02), and a significantly shorter time t

288 n was worse in BKV-nephropathy compared with BKV-negative patients beginning at transplantation.

289 Then the percentage of HRPTEC infected with BKV by immunofluorescent analysis and large T-antigen ex

290 l blood mononuclear cells were infected with BKV Dunlop strain or other viruses.

291 high prevalence of persistent infection with BKV in the general population, it is possible that eithe

292 Reduced survival was noted for patients with BKV infection (P=0.03).

293 hose without infection, but in patients with BKV infection, creatinine clearances were lower at times

294 to validate the use of IVIG in patients with BKV infection.

295 even on a separate analysis of patients with BKV load 1E+07 copies per mL or less.

296 nificantly higher at 1 year in patients with BKV replication.

297 V had a higher prevalence in recipients with BKV nephropathy than in those with viruria and viremia (

298 ected from a total of 251 RTRs (71 RTRs with BKV infection and 180 without BKV infection).

299 recipients at our center were screened with BKV plasma PCR monthly for the first 4 months posttransp

300 (71 RTRs with BKV infection and 180 without BKV infection).