ライフサイエンスコーパス: WHV

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

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

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

4 WHV EnII is recognized by at least three host transcript

5 WHV replication was up-regulated by dexamethasone treatm

6 WHV-infected hepatocytes from chronic carrier woodchucks

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

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

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

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

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

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

13 ocumented in some woodchucks following acute WHV infection.

14 actic vaccination and in recovery from acute WHV infection.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

45 atocarcinogenesis of woodchucks with chronic WHV infection.

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

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

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

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

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

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

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

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

54 nce chronicity as an outcome of experimental WHV infection.

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

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

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

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

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

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

61 at determine resolution versus chronicity in WHV infection.

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

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

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

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

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

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

68 nimals were later challenged with infectious WHV.

69 line 203 with leucine dramatically inhibited WHV production.

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

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

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

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

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

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

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

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

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

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

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

81 I was associated with resolution of neonatal WHV infection.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

103 chucks resulted in transient reactivation of WHV replication.

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

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

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

107 onates were inoculated with the W8 strain of WHV.

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

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

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

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

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

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

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

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

116 o those woodchucks progressing to persistent WHV infection.

117 tes isolated from woodchucks with persistent WHV infection.

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

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

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

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

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

123 Serum WHV collected during acute infection was compared to vir

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

176 ollowing neonatal woodchuck hepatitis virus (WHV) infection.

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

178 chronic neonatal woodchuck hepatitis virus (WHV) infection.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

202 ks (Marmota monax) chronically infected with WHV.

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

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

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