ライフサイエンスコーパス: WHV

1 WHV assembly shows similar susceptibility to HBV antivir

2 WHV DNA integrations were demonstrated in 43% but none h

3 WHV En II activity is strongly liver specific and maps t

4 WHV enhancer II (En II) is the major cis-acting element

5 WHV EnII is recognized by at least three host transcript

6 WHV replication was up-regulated by dexamethasone treatm

7 WHV-infected hepatocytes from chronic carrier woodchucks

8 WHV-infected woodchucks received eight weekly oral doses

9 Frozen liver samples from 20 (17 WHV-infected and 3 noninfected) woodchucks, 10 with WHV-

10 s paper, we present a cryo-EM structure of a WHV capsid showing its similarity to HBV.

11 on, we examined the in vivo infectivity of a WHV genome bearing a naturally occurring single amino ac

12 ype, we knocked out N-myc expression using a WHV-N-myc1 antisense vector.

13 erinfected with HDV, they produce HDV with a WHV envelope, wHDV.

14 s, and Th1-type cytokines, suggesting active WHV-specific T lymphocytes.

15 ocumented in some woodchucks following acute WHV infection.

16 actic vaccination and in recovery from acute WHV infection.

17 racts derived from primary cultures of acute WHV-infected hepatocytes.

18 between the production of antibodies against WHV surface antigens and parameters of WHV infection app

19 rt, the antiviral activity of l-FMAU against WHV replication in chronically infected woodchucks is de

20 e treatment of chronic HBV infection against WHV replication in chronically infected woodchucks.

21 Although WHV envelope, core, and X proteins were produced in the

22 epatic tumors from X/c-myc bitransgenics and WHV-infected woodchucks.

23 ce antigens, in HBV-infected chimpanzees and WHV-infected woodchucks revealed multiple distinct phase

24 Purified HBV and WHV Cp spontaneously assemble into 120-dimer capsids.

25 e organization and the structures of HBV and WHV spherical SVPs.

26 n, DNA polymerase, and pgRNA between HBV and WHV suggest that HBV capsid protein confers sensitivity

27 nd immunogenic compatibility between HBV and WHV, equivalence in immune responses in different forms

28 lication of wild-type and X-negative HBV and WHV.

29 nal response to persistent WHV infection and WHV-induced HCC.

30 n [WHcrAg]) include the WHV core protein and WHV e antigen (WHeAg) as well as the WHV PreC protein (W

31 epatic and peripheral Treg in uninfected and WHV chronically infected woodchucks showed a significant

32 Livers from uninfected and WHV-infected woodchucks were examined to determine if pg

33 omas (HCCs), were superinfected with another WHV strain, WHVNY.

34 he recombinant adenovirus-HBV or baculovirus-WHV, the replication level of the X-negative construct w

35 all were grade 2 or 3 HCCs, and in 83%, both WHV DNA integrations and N-myc rearrangements were demon

36 A key step in hepatocarcinogenesis by WHV is insertional activation of the cellular N-myc gene

37 WHV RNA and covalently closed circular (ccc)WHV-DNA levels also were observed.

38 pecimens obtained postmortem from 13 chronic WHV carriers were analyzed and the frequency of WHV DNA

39 Almost all woodchucks that become chronic WHV carriers after experimental neonatal inoculation dev

40 r the conditions used, does not cure chronic WHV infections.

41 mental results more firmly establish chronic WHV infection in woodchucks as an accurate and predictiv

42 tochemical examination of liver from chronic WHV-infected animals showed WHV core antigen (WHcAg) and

43 Furthermore, chronic WHV infection in woodchucks usually leads to development

44 nd cell-mediated immune tolerance in chronic WHV infection, but the combination with drug was more ef

45 added benefit over IL-12 therapy in chronic WHV infection.

46 he onset and maintenance of neonatal chronic WHV infection are not associated with antagonistic type

47 tored the T-cell response profile of chronic WHV carrier woodchucks to that seen in prophylactic vacc

48 -beta) were detected in the liver of chronic WHV carriers in comparison to uninfected animals.

49 suppressive reaction in the liver of chronic WHV carriers that counteracts the antiviral effect of th

50 having occurred during the period of chronic WHV infection ( approximately 1.5 years) in these animal

51 This revealed that chronic WHV infection, like HBV, is associated with (1) a limite

52 atocarcinogenesis of woodchucks with chronic WHV infection.

53 he integrated WHV DNA contained the complete WHV X gene (WHx) and its promoter; however, we did not d

54 ealed that all of the tumors which contained WHV replication intermediates were also positive for WHx

55 ome using a chimeric form of hHDV containing WHV S protein, again supporting the essential role of pr

56 The highly rearranged WHV DNA contains WHV enhancers which activate the N-myc promoter, and a h

57 d with the strain WHV7 and already developed WHV-induced hepatocellular carcinomas (HCCs), were super

58 tion and also provide a means for developing WHV carriers for therapeutic studies.

59 rtional activation of the N-myc2 gene during WHV hepatocarcinogenesis.

60 irus (WHV) precore/core gene products (i.e., WHV core-related antigen [WHcrAg]) include the WHV core

61 ficant dose dependent decreases in enveloped WHV, resulting in undetectable amounts in some cases.

62 nce chronicity as an outcome of experimental WHV infection.

63 erum of 1 woodchuck that became positive for WHV DNA during immunosuppression was inoculated into WHV

64 ction was compared to virions harvested from WHV-infected woodchucks during either (i) early chronic

65 pgp in HCCs compared with normal liver from WHV-infected woodchucks.

66 Twenty grade 2 HCCs had WHV DNA integrations in 80% and in 38% N-myc rearrangeme

67 Like HBV, WHV infects the liver and can cause acute and chronic he

68 e by conventional dot-blot analysis, hepatic WHV-DNA replicative intermediates (RI) had decreased 100

69 Though they have 65% identity, WHV Cp has error-prone assembly with stronger protein-pr

70 at determine resolution versus chronicity in WHV infection.

71 mounts of WHV empty virions were detected in WHV-infected woodchuck serum.

72 reater than four orders of magnitude drop in WHV titer in response to interferon alpha treatment.

73 d by analysis of the recombination joints in WHV cccDNA.

74 , with greater than 1,000-fold reductions in WHV-DNA serum levels observed after as little as 2 to 3

75 can induce a sustained antiviral response in WHV-infected woodchucks; the identification of a baselin

76 voted to the regulation of pregenomic RNA in WHV, (ii) HNF-1 is essential for EnII function in vivo,

77 e ddG in reducing WHV-DNA levels in serum in WHV-infected woodchucks.

78 mpounds used in clinical anti-HBV studies in WHV-infected woodchucks, thereby making interpretations

79 nimals were later challenged with infectious WHV.

80 line 203 with leucine dramatically inhibited WHV production.

81 and provide a direct function for integrated WHV DNA in hepatocarcinogenesis.

82 The integrated WHV DNA contained the complete WHV X gene (WHx) and its

83 Because cells with integrated WHV DNA comprised only 1-2% of total liver cells, it is

84 during immunosuppression was inoculated into WHV-susceptible woodchucks, and a productive infection w

85 uced depressions in viremia and intrahepatic WHV-DNA replication that were consistent with their rela

86 y reduced viremia, antigenemia, intrahepatic WHV replication, and intrahepatic expression of woodchuc

87 most cases with lower levels of intrahepatic WHV covalently closed circular DNA (cccDNA).

88 g/d), significant reductions of intrahepatic WHV RNA and covalently closed circular (ccc)WHV-DNA leve

89 GS-9688 treatment reduced intrahepatic WHV RNA and DNA levels by >95% in animals in which the a

90 cine resembled that observed in self-limited WHV infection.

91 vate the N-myc promoter, and a hybrid N-myc1-WHV mRNA is produced, which leads to a high steady-state

92 oad and chronicity as an outcome of neonatal WHV infection result from a temporal deficiency in the a

93 I was associated with resolution of neonatal WHV infection.

94 In a second experiment, groups of nine WHV carriers or uninfected woodchucks were given 1.5 mg/

95 nts of N-myc were detected in the absence of WHV DNA integrations.

96 -glycosylated, and no significant amounts of WHV empty virions were detected in WHV-infected woodchuc

97 Cells of WHV-induced HCCs are susceptible to HDV infection in viv

98 enes (ISG) may play a role in the control of WHV replication.

99 CDMS) is used to measure the distribution of WHV assembly products.

100 ccumulation of serum relaxed circular DNA of WHV demonstrated that the virions produced during early

101 Sequences of the assembly domain of WHV and HBV core proteins (wCp149 and hCp149, respective

102 ecreased 100-fold, and hepatic expression of WHV core antigen was remarkably decreased.

103 carriers were analyzed and the frequency of WHV DNA integrations and of N-myc rearrangements compare

104 X gene (WHx) is required for infectivity of WHV in woodchucks, and the gene encodes a broadly acting

105 cell DNA junctions created by integration of WHV and present following recovery in the livers of WHV-

106 Twenty-four grade 3 HCCs had integrations of WHV DNA in 79% and N-myc rearrangements in 74%.

107 immune response was observed in the liver of WHV-replicating mice.

108 present following recovery in the livers of WHV-infected control or ETV-treated woodchucks.

109 the analysis of such intrahepatic markers of WHV infection as replicative intermediate DNA, covalentl

110 we surveyed livers and HCCs from a panel of WHV carrier woodchucks for the presence of WHx by utiliz

111 ainst WHV surface antigens and parameters of WHV infection appears to be complex.

112 r DNA, pregenomic RNA, and the percentage of WHV core antigen-positive hepatocytes measured at severa

113 Unlike human HBV, the capsid protein of WHV has evolved to function in a nonhomeostatic environm

114 eleted this region from the pre-S protein of WHV or mutated individual amino acids within the region.

115 d that the hhr region of the core protein of WHV was critical for capsid assembly.

116 chucks resulted in transient reactivation of WHV replication.

117 uired for virus assembly and/or secretion of WHV.

118 ally as adenomas and integrated sequences of WHV DNA were detected in two of the four tumor nodules.

119 When inserted into a laboratory strain of WHV, each of the mutations, or combinations of mutations

120 onates were inoculated with the W8 strain of WHV.

121 his resolution, the T=4 capsid structures of WHV and HBV are practically identical.

122 Furthermore, treatment of WHV-infected animals with an adenovirus encoding IL-12 f

123 All tested types of WHV inoculum were related, because they were collected f

124 hymidine (AZT [zidovudine]) had no effect on WHV replication in these studies.

125 baculoviruses expressing replicating HBV or WHV genomes have been developed as a robust and convenie

126 ion of the X-negative virus of either HBV or WHV was enhanced and restored to the wild-type level.

127 mutations were also tested in an overlength WHV genome for their impact on viral replication and gen

128 d the transcriptional response to persistent WHV infection and WHV-induced HCC.

129 o those woodchucks progressing to persistent WHV infection.

130 tes isolated from woodchucks with persistent WHV infection.

131 At N-nonyl-DNJ concentrations that prevented WHV secretion, the glycosylation of most serum glycoprot

132 o, and therefore express functional putative WHV receptors and support the steps of the attachment/en

133 The highly rearranged WHV DNA contains WHV enhancers which activate the N-myc

134 0) reduction in serum viral load and reduced WHV surface antigen (WHsAg) levels to below the limit of

135 lly more effective than free ddG in reducing WHV-DNA levels in serum in WHV-infected woodchucks.

136 ce of B or T cell-mediated immune responses, WHV establishes a persistent noncytotoxic infection of w

137 Serum WHV collected during acute infection was compared to vir

138 en in most carriers but did not affect serum WHV DNA and surface antigen.

139 rs treated first with L-FMAU to reduce serum WHV DNA and surface antigen and then vaccinated had a si

140 he fourth week, while free ddG reduced serum WHV DNA by 2.2- to 10.4-fold.

141 Liposomal DPP-ddG reduced serum WHV DNA by 23- to 46-fold at the end of the fourth week,

142 After 4 weeks, the serum WHV-DNA concentration in the FIAU-treated carrier group

143 After 12 weeks of FIAU treatment, serum WHV DNA was not detectable by conventional dot-blot anal

144 h woodchuck hepatitis virus (WHV) and showed WHV replication for at least 10 months with titers up to

145 ver from chronic WHV-infected animals showed WHV core antigen (WHcAg) and WHxAg expression in non-neo

146 e for anti-WHs 3-6 years later, but in some, WHV DNA was detected in serum, liver, and/or peripheral

147 chuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a

148 This revealed that WHV does not induce significant intrahepatic gene expres

149 ein and WHV e antigen (WHeAg) as well as the WHV PreC protein (WPreC) in infected woodchucks.

150 f other experimental antiviral agents in the WHV/woodchuck model system.

151 V core-related antigen [WHcrAg]) include the WHV core protein and WHV e antigen (WHeAg) as well as th

152 sion of the DHBV molecular equivalent of the WHV and HBV DN constructs inhibited wild-type DHBV repli

153 ly promoting conditions, roughly half of the WHV assembly products are T=4 capsids composed of exactl

154 ectron microscopy (cryo-EM) structure of the WHV capsid at nanometer resolution and characterization

155 We determined the structures of the WHV capsid to 4.5- angstrom resolution by cryo-electron

156 ryo-electron microscopy (cryo-EM) and of the WHV Cp dimer to 2.9- angstrom resolution by crystallogra

157 t epitopes of the pre-S and S regions of the WHV envelope protein.

158 suggested that persistence of several of the WHV mutants as prevalent species in the serum and, by in

159 One week after surgery the WHV carrier woodchucks were superinfected with WHV-envel

160 s determined entirely by pre-S1 and that the WHV and HBV pre-S1 proteins recognize different receptor

161 in the woodchuck hepatitis virus (WHV) (the WHV posttranscriptional regulatory element [WPRE]) has t

162 nse of peripheral blood mononuclear cells to WHV peptides.

163 after infection durable cellular immunity to WHV is essential for the long-term control of viral repl

164 g woodchucks had robust, acute-phase vCMI to WHV antigens (core, surface, and x) and to several nonov

165 that was still well below that of wild-type WHV in the absence of the drug.

166 viral DNA nearly as efficiently as wild-type WHV.

167 was demonstrated by the detection of unique WHV DNA integration patterns in hepatocellular carcinoma

168 VNY superinfection was demonstrated by using WHV strain-specific PCR assays and (i) finding WHVNY rel

169 ment found in the woodchuck hepatitis virus (WHV) (the WHV posttranscriptional regulatory element [WP

170 with HBV-related woodchuck hepatitis virus (WHV) and already developed HCCs were used as an experime

171 aviruses, such as woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV).

172 The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmot

173 The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmot

174 ic infection with woodchuck hepatitis virus (WHV) and serve as a model of hepatitis B virus-associate

175 e infectable with woodchuck hepatitis virus (WHV) and showed WHV replication for at least 10 months w

176 icient mutants of woodchuck hepatitis virus (WHV) are not completely replication defective, possibly

177 lly infected with woodchuck hepatitis virus (WHV) are superinfected with HDV, they produce HDV with a

178 mentally with the woodchuck hepatitis virus (WHV) at 3 days of age.

179 ps of six chronic woodchuck hepatitis virus (WHV) carrier woodchucks received daily doses of FIAU by

180 ted at birth with woodchuck hepatitis virus (WHV) cleared viremia and developed antibodies to surface

181 lly infected with woodchuck hepatitis virus (WHV) contained covalently closed circular DNA (cccDNA) m

182 capsid protein of woodchuck hepatitis virus (WHV) contains four hydrophobic residues, including leuci

183 ) and the related woodchuck hepatitis virus (WHV) determined by cryo-electron microscopy in combinati

184 Integrations of woodchuck hepatitis virus (WHV) DNA and rearrangements of the N-myc 2 gene have bee

185 contain a single woodchuck hepatitis virus (WHV) DNA integration in the 3' untranslated region of ex

186 described HBV and woodchuck hepatitis virus (WHV) dominant negative (DN) core mutants that were capab

187 Woodchuck hepatitis virus (WHV) efficiently induces hepatocellular carcinoma in chr

188 infected with the woodchuck hepatitis virus (WHV) elicited differential T-cell response profiles depe

189 Woodchuck hepatitis virus (WHV) enhancer II (EnII) is located upstream of the major

190 lly infected with woodchuck hepatitis virus (WHV) for 4 weeks by intraperitoneal injection of 2.6 mum

191 velope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Al

192 lly infected with woodchuck hepatitis virus (WHV) induces a transient decline in virus titers.

193 ith self-limiting woodchuck hepatitis virus (WHV) infection to those woodchucks progressing to persis

194 ther markers of a woodchuck hepatitis virus (WHV) infection using rabbit antisera generated against r

195 ucks with chronic woodchuck hepatitis virus (WHV) infection was assayed for randomly integrated viral

196 chronic neonatal woodchuck hepatitis virus (WHV) infection.

197 ollowing neonatal woodchuck hepatitis virus (WHV) infection.

198 ing the course of woodchuck hepatitis virus (WHV) infection.

199 ance of transient woodchuck hepatitis virus (WHV) infections.

200 ordingly, several woodchuck hepatitis virus (WHV) inocula were characterized.

201 Woodchuck hepatitis virus (WHV) is prone to aberrant assembly in vitro and can form

202 we found that the woodchuck hepatitis virus (WHV) precore/core gene products (i.e., WHV core-related

203 infected with the woodchuck hepatitis virus (WHV) represent the best animal model for chronic hepatit

204 rmota monax) with woodchuck hepatitis virus (WHV) represents the most valuable immunopathogenic model

205 city of an analog woodchuck hepatitis virus (WHV) surface antigen (WHsAg) pDNA vaccine was studied in

206 of the virions of woodchuck hepatitis virus (WHV) to induce productive acute infection in naive adult

207 lly infected with woodchuck hepatitis virus (WHV) were treated with N-nonyl-deoxynojirimycin (N-nonyl

208 infected with the woodchuck hepatitis virus (WHV) were treated with the antiviral drug 1-(2-fluoro-5-

209 The woodchuck hepatitis virus (WHV) X gene (WHx) is required for infectivity of WHV in

210 rated a series of woodchuck hepatitis virus (WHV) X mutants, including mutants of the domain interact

211 the stability of woodchuck hepatitis virus (WHV) X protein (WHx) in primary hepatocytes isolated fro

212 Woodchuck hepatitis virus (WHV), a close relative of human hepatitis B virus (HBV),

213 lly infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to hepatitis B viru

214 lly infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepati

215 0 million people; woodchuck hepatitis virus (WHV), an HBV homologue, has been an important model syst

216 ted hepadnavirus, woodchuck hepatitis virus (WHV), serve as a model for HBV because woodchucks chroni

217 lly infected with woodchuck hepatitis virus (WHV), we investigated the consequences of combining lami

218 e closely related woodchuck hepatitis virus (WHV), which has been shown to lack a functional enhancer

219 ere obtained from woodchuck hepatitis virus (WHV)-infected neonatal woodchucks at 2 time points befor

220 ansgenic mice and woodchuck hepatitis virus (WHV)-infected woodchucks.

221 BV or HBV-related woodchuck hepatitis virus (WHV).

222 bors a DNA virus (Woodchuck hepatitis virus [WHV]) that is similar in structure and replicative life

223 ing either (i) early chronic infection, when WHV-induced hepatocellular carcinoma (HCC) was not yet d

224 ected and 3 noninfected) woodchucks, 10 with WHV-associated hepatic tumors and 10 without tumors, wer

225 because woodchucks chronically infected with WHV also develop hepatocellular carcinomas.

226 ks (Marmota monax) chronically infected with WHV.

227 om woodchucks experimentally inoculated with WHV were examined during the acute phase of infection an

228 V carrier woodchucks were superinfected with WHV-enveloped HDV (wHDV).

229 Those with WHV DNA had increased in vitro cellular immune responses

230 Woodchuck-WHV infection offers a well-characterized and all-inclus