scholarly journals Antiviral effect of hepatitis B virus S/C gene loci antisense locked nucleic acid on transgenic mice in vivo

2015 ◽  
Vol 14 (3) ◽  
pp. 10087-10095 ◽  
Author(s):  
Y.B. Deng ◽  
H.J. Qin ◽  
Y.H. Luo ◽  
Z.R. Liang ◽  
J.J. Zou
Keyword(s):  
Hepatitis B Virus ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Antiviral Effect ◽  
Locked Nucleic Acid ◽  
B Virus

scholarly journals Antiviral effect of hepatitis B virus S gene-specific anti-gene locked nucleic acid in hepatitis B virus transgenic mice

2017 ◽  
Vol 25 (31) ◽  
pp. 2782-2790
Author(s):  
Shu-Rong Xiao ◽  
Gui-Dan Xu ◽  
Wu-Jun Wei ◽  
Bin Peng ◽  
Yi-Bin Deng
Keyword(s):  
Hepatitis B Virus ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Antiviral Effect ◽  
Locked Nucleic Acid ◽  
S Gene ◽  
B Virus

scholarly journals Antiviral effects of hepatitis B virus S gene-specific anti-gene locked nucleic acid in transgenic mice

2018 ◽  
Vol 6 (8) ◽  
pp. 183-191
Author(s):  
Shu-Rong Xiao ◽  
Gui-Dan Xu ◽  
Wu-Jun Wei ◽  
Bin Peng ◽  
Yi-Bin Deng
Keyword(s):  
Hepatitis B Virus ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Locked Nucleic Acid ◽  
S Gene ◽  
Antiviral Effects ◽  
B Virus

scholarly journals Inhibition of Cellular Proteasome Activities Mediates HBX-Independent Hepatitis B Virus Replication In Vivo

2010 ◽  
Vol 84 (18) ◽  
pp. 9326-9331 ◽  
Author(s):  
Zhensheng Zhang ◽  
Eun Sun ◽  
Jing-hsiung James Ou ◽  
T. Jake Liang
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Productive Infection ◽  
Minor Effect ◽  
Hbv Replication ◽  
B Virus ◽  
Culture Models ◽  
A Minor

ABSTRACT The X protein (HBX) of the hepatitis B virus (HBV) is essential for HBV productive infection in vivo. Our previous study (Z. Hu, Z. Zhang, E. Doo, O. Coux, A. L. Goldberg, and T. J. Liang, J. Virol. 73:7231-7240, 1999) shows that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. Previously, we demonstrated that HBX affects hepadnaviral replication through a proteasome-dependent pathway in cell culture models. In the present study, we studied the effect of the proteasome inhibitor MLN-273 in two HBV mouse models. We demonstrated that administration of MLN-273 to transgenic mice containing the replication-competent HBV genome with the defective HBX gene substantially enhanced HBV replication, while the compound had a minor effect on wild-type HBV transgenic mice. Similar results were obtained by using C57BL/6 mice infected with recombinant adenoviruses expressing the replicating HBV genome. Our data suggest that HBV replication is subjected to regulation by cellular proteasome and HBX functions through the inhibition of proteasome activities to enhance HBV replication in vivo.

scholarly journals Expression of Hepatitis B Virus X Protein Does Not Alter the Accumulation of Spontaneous Mutations in Transgenic Mice

2000 ◽  
Vol 74 (11) ◽  
pp. 5266-5272 ◽  
Author(s):  
Charles R. Madden ◽  
Milton J. Finegold ◽  
Betty L. Slagle
Keyword(s):  
Dna Repair ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Spontaneous Mutations ◽  
Environmental Carcinogens ◽  
X Protein ◽  
B Virus ◽  
The Impact

ABSTRACT Chronic infection with hepatitis B virus (HBV) is one of the major etiological factors in the development of human hepatocellular carcinoma. Transgenic mice that express the HBV X protein (HBx) have previously been shown to be more sensitive to the effects of hepatocarcinogens, although the mechanism for this cofactor role remains unknown. The ability of HBx to inhibit DNA repair in transiently transfected cell lines suggests one possible pathway. In the present study, primary hepatocytes isolated from transgenic mice that possess the HBV X gene under the control of the human α-1-antitrypsin regulatory region (ATX mice) were found to be deficient in their ability to conduct unscheduled DNA synthesis in response to UV-induced DNA damage. In order to measure the impact of HBx expression on DNA repair in vivo, double-transgenic mice that express HBx and possess a bacteriophage lambda transgene were sacrificed at 30, 90, and 240 days of age. Mutation frequency was determined for high-molecular-weight liver DNA of ATX and control mice by functional analysis of the lambda transgene. Expression of HBx did not significantly increase the accumulation of spontaneous mutations. These results are consistent with previous studies of HBx transgenic mice in which no effect of HBx on liver histology was apparent. This new animal model provides a powerful system in which to investigate the in vivo cooperation between HBx expression and environmental carcinogens.

scholarly journals Hepatocyte Nuclear Factor 3β Inhibits Hepatitis B Virus Replication In Vivo

2002 ◽  
Vol 76 (24) ◽  
pp. 12974-12980 ◽  
Author(s):  
Krista E. Banks ◽  
Aimee L. Anderson ◽  
Hong Tang ◽  
Douglas E. Hughes ◽  
Robert H. Costa ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
B Virus ◽  
Chronic Hbv ◽  
Replication Intermediates

ABSTRACT Hepatitis B virus (HBV) transgenic mice expressing rat hepatocyte nuclear factor 3β (HNF3β) were generated by breeding HBV transgenic mice with transgenic mice that constitutively overexpress the rat HNF3β polypeptide in the liver. HBV 3.5-, 2.4- and 2.1-kb transcripts were reduced 2- to 4-fold in these mice relative to the HBV transgenic mouse controls. In contrast, the abundance of viral replication intermediates was profoundly reduced in HBV transgenic mice by overexpression of HNF3β. This results, in part, from the preferential reduction in the level of the pregenomic 3.5-kb RNA relative to the precore 3.5-kb RNA. Therefore, it is apparent that increased expression of HNF3β modestly reduces viral transcription and dramatically inhibits replication in vivo in the HBV transgenic mouse. This suggests that altering the activity of this transcription factor in vivo in chronic HBV carriers might be therapeutically beneficial.

scholarly journals Nuclear Covalently Closed Circular Viral Genomic DNA in the Liver of Hepatocyte Nuclear Factor 1α-Null Hepatitis B Virus Transgenic Mice

2001 ◽  
Vol 75 (6) ◽  
pp. 2900-2911 ◽  
Author(s):  
Anneke K. Raney ◽  
Carrie M. Eggers ◽  
Eric F. Kline ◽  
Luca G. Guidotti ◽  
Marco Pontoglio ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Genomic Dna ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
B Virus ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Replication Intermediates

ABSTRACT The role of hepatocyte nuclear factor 1α (HNF1α) in the regulation of hepatitis B virus (HBV) transcription and replication in vivo was investigated using a HNF1α-null HBV transgenic mouse model. HBV transcription was not measurably affected by the absence of the HNF1α transcription factor. However, intracellular viral replication intermediates were increased two- to fourfold in mice lacking functional HNF1α protein. The increase in encapsidated cytoplasmic replication intermediates in HNF1α-null HBV transgenic mice was associated with the appearance of nonencapsidated nuclear covalently closed circular (CCC) viral genomic DNA. Viral CCC DNA was not readily detected in HNF1α-expressing HBV transgenic mice. This indicates the synthesis of nuclear HBV CCC DNA, the proposed viral transcriptional template found in natural infection, is regulated either by subtle alterations in the levels of viral transcripts or by changes in the physiological state of the hepatocyte in this in vivo model of HBV replication.

scholarly journals Therapeutic Antiviral Effect of the Nucleic Acid Polymer REP 2055 against Persistent Duck Hepatitis B Virus Infection

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0140909 ◽  
Author(s):  
Faseeha Noordeen ◽  
Catherine A. Scougall ◽  
Arend Grosse ◽  
Qiao Qiao ◽  
Behzad B. Ajilian ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Nucleic Acid ◽  
Virus Infection ◽  
Hepatitis B ◽  
Antiviral Effect ◽  
Hepatitis B Virus Infection ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

scholarly journals Alkoxyalkyl Esters of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent and Selective Inhibitors of Hepatitis B Virus (HBV) Replication In Vitro and in HBV Transgenic Mice In Vivo

2009 ◽  
Vol 53 (7) ◽  
pp. 2865-2870 ◽  
Author(s):  
John D. Morrey ◽  
Brent E. Korba ◽  
James R. Beadle ◽  
David L. Wyles ◽  
Karl Y. Hostetler
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Transgenic Mice ◽  
Adefovir Dipivoxil ◽  
Murine Cytomegalovirus ◽  
Cross Resistance ◽  
B Virus

ABSTRACT Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (S)-HPMPA, we prepared the hexadecyloxypropyl (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters and compared their activities with the activity of adefovir dipivoxil in vitro and in vivo. Alkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more active than unmodified (S)-HPMPA on the basis of their 50% effective concentrations in 2.2.15 cells. The increased antiviral activity appeared to be due in part to the increased uptake and conversion of HDP-(S)-HPMPA to HPMPA diphosphate observed in HepG2 cells in vitro. HDP-(S)-HPMPA retained full activity against HBV mutants resistant to lamivudine (L180M, M204V), but cross-resistance to a mutant resistant to adefovir (N236T) was detected. HDP-(S)-HPMPA is orally bioavailable and provides excellent liver exposure to the drug. Oral treatment of HBV transgenic mice with HDP-(S)-HPMPA, 15M-HDP-(S)-HPMPA, and ODE-(S)-HPMPA for 14 days reduced liver HBV DNA levels by roughly 1.5 log units, a response equivalent to that of adefovir dipivoxil.

scholarly journals In Vivo Regulation of Hepatitis B Virus Replication by Peroxisome Proliferators

1999 ◽  
Vol 73 (12) ◽  
pp. 10377-10386 ◽  
Author(s):  
Luca G. Guidotti ◽  
Carrie M. Eggers ◽  
Anneke K. Raney ◽  
Susan Y. Chi ◽  
Jeffrey M. Peters ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Fold Increase ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferators ◽  
B Virus ◽  
Replication Intermediates ◽  
Transcription And Replication

ABSTRACT The role of the peroxisome proliferator-activated receptor α (PPARα) in regulating hepatitis B virus (HBV) transcription and replication in vivo was investigated in an HBV transgenic mouse model. Treatment of HBV transgenic mice with the peroxisome proliferators Wy-14,643 and clofibric acid resulted in a less than twofold increase in HBV transcription rates and steady-state levels of HBV RNAs in the livers of these mice. In male mice, this increase in transcription was associated with a 2- to 3-fold increase in replication intermediates, whereas in female mice it was associated with a 7- to 14-fold increase in replication intermediates. The observed increases in transcription and replication were dependent on PPARα. HBV transgenic mice lacking this nuclear hormone receptor showed similar levels of HBV transcripts and replication intermediates as untreated HBV transgenic mice expressing PPARα but failed to demonstrate alterations in either RNA or DNA synthesis in response to peroxisome proliferators. Therefore, it appears that very modest alterations in transcription can, under certain circumstances, result in relatively large increases in HBV replication in HBV transgenic mice.

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