scholarly journals In Vivo Mouse Models for Hepatitis B Virus Infection and Their Application

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanqin Du ◽  
Ruth Broering ◽  
Xiaoran Li ◽  
Xiaoyong Zhang ◽  
Jia Liu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mouse Model ◽  
Mouse Models ◽  
Viral Vector ◽  
Hbv Infection ◽  
Research Progress ◽  
Hydrodynamic Injection ◽  
B Virus

Despite the availability of effective vaccination, hepatitis B virus (HBV) infection continues to be a major challenge worldwide. Research efforts are ongoing to find an effective cure for the estimated 250 million people chronically infected by HBV in recent years. The exceptionally limited host spectrum of HBV has limited the research progress. Thus, different HBV mouse models have been developed and used for studies on infection, immune responses, pathogenesis, and antiviral therapies. However, these mouse models have great limitations as no spread of HBV infection occurs in the mouse liver and no or only very mild hepatitis is present. Thus, the suitability of these mouse models for a given issue and the interpretation of the results need to be critically assessed. This review summarizes the currently available mouse models for HBV research, including hydrodynamic injection, viral vector-mediated transfection, recombinant covalently closed circular DNA (rc-cccDNA), transgenic, and liver humanized mouse models. We systematically discuss the characteristics of each model, with the main focus on hydrodynamic injection mouse model. The usefulness and limitations of each mouse model are discussed based on the published studies. This review summarizes the facts for considerations of the use and suitability of mouse model in future HBV studies.

316 IMMUNOSUPPRESSION MODULATES THE COURSE OF HEPATITIS B VIRUS (HBV) INFECTION IN HYDRODYNAMIC INJECTION MOUSE MODEL

2011 ◽  
Vol 54 ◽  
pp. S127
Author(s):  
J.Z. Wang ◽  
B.J. Wang ◽  
S.M. Huang ◽  
J. Wu ◽  
Z.N. Zhu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mouse Model ◽  
Hbv Infection ◽  
Hydrodynamic Injection ◽  
B Virus

A nude mouse model for the in vivo production of hepatitis B virus

1990 ◽  
Vol 98 (2) ◽  
pp. 470-477 ◽  
Author(s):  
Wei-Rong Zhai ◽  
Gabor Vajta ◽  
George Acs ◽  
Fiorenzo Paronetto
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mouse Model ◽  
Nude Mouse ◽  
Nude Mouse Model ◽  
B Virus

scholarly journals Immunogenicity and Tolerogenicity of Hepatitis B Virus Structural and Nonstructural Proteins: Implications for Immunotherapy of Persistent Viral Infections

2002 ◽  
Vol 76 (17) ◽  
pp. 8609-8620 ◽  
Author(s):  
Kazuhiro Kakimi ◽  
Masanori Isogawa ◽  
JoSan Chung ◽  
Alessandro Sette ◽  
Francis V. Chisari
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Infections ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response ◽  
Hbv Infection ◽  
Peripheral Tolerance ◽  
Specific Ctls ◽  
B Virus

ABSTRACT Persistent hepatitis B virus (HBV) infection is characterized by a weak and narrowly focused CD8+ T-cell response to HBV that is thought to reflect the induction of central and/or peripheral tolerance to HBV proteins in neonatal and adult onset infections, respectively. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may lead to viral clearance in chronically infected individuals. The present study was performed to compare the relative immunogenicities and tolerogenicities of HBV structural (envelope [ENV]) and nonstructural (polymerase [POL]) proteins at the CD8+ cytotoxic T lymphocyte (CTL) level in transgenic mice that replicate HBV in the liver and secrete infectious virus into the blood, thus representing an excellent model of persistent HBV infection. Interestingly, the mice were tolerant to the ENV but not to the POL proteins at the CTL level. Furthermore, the POL-specific CTLs had no impact on HBV replication or liver function in vivo, even though they were readily induced and reached the liver after DNA immunization, reflecting their relatively low avidity and the low level at which the POL protein is expressed by the hepatocyte. Collectively, these results suggest that the factors that make POL less tolerogenic also make POL-specific CTLs relatively inefficient effector cells when they reach the target organ. Immunotherapeutic strategies to control HBV infection by inducing virus-specific CTL responses in chronically infected subjects should be evaluated in light of this observation.

scholarly journals Evaluation of Single and Combination Therapies with Tenofovir Disoproxil Fumarate and EmtricitabineIn Vitroand in a Robust Mouse Model Supporting High Levels of Hepatitis B Virus Replication

2012 ◽  
Vol 56 (12) ◽  
pp. 6186-6191 ◽  
Author(s):  
Raymond F. Schinazi ◽  
Leda Bassit ◽  
Marcia M. Clayton ◽  
Bill Sun ◽  
James J. Kohler ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Combination Therapy ◽  
Virus Replication ◽  
Tenofovir Disoproxil Fumarate ◽  
Hbv Infection ◽  
Experimental Drugs ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACTNext-generation therapies for chronic hepatitis B virus (HBV) infection will involve combinations of established and/or experimental drugs. The current study investigated thein vitroandin vivoefficacy of tenofovir disoproxil fumarate (TDF) and/or emtricitabine [(−)-FTC] alone and in combination therapy for HBV infection utilizing the HepAD38 system (human hepatoblastoma cells transfected with HBV). Cellular pharmacology studies demonstrated increased levels of (−)-FTC triphosphate with coincubation of increasing concentrations of TDF, while (−)-FTC had no effect on intracellular tenofovir (TFV) diphosphate levels. Quantification of extracellular HBV by real-time PCR from hepatocytes demonstrated the anti-HBV activity with TDF, (−)-FTC, and their combination. Combination of (−)-FTC with TDF or TFV (ratio, 1:1) had a weighted average combination index of 0.7 for both combination sets, indicating synergistic antiviral effects. No cytotoxic effects were observed with any regimens. Using anin vivomurine model which develops robust HBV viremia in nude mice subcutaneously injected with HepAD38 cells, TDF (33 to 300 mg/kg of body weight/day) suppressed virus replication for up to 10 days posttreatment. At 300 mg/kg/day, (−)-FTC strongly suppressed virus titers to up to 14 days posttreatment. Combination therapy (33 mg/kg/day each drug) sustained suppression of virus titer/ml serum (<1 log10unit from pretreatment levels) at 14 days posttreatment, while single-drug treatments yielded virus titers 1.5 to 2 log units above the initial virus titers. There was no difference in mean alanine aminotransferase values or mean wet tumor weights for any of the groups, suggesting a lack of drug toxicity. TDF–(−)-FTC combination therapy provides more effective HBV suppression than therapy with each drug alone.

scholarly journals Poly(I:C) Treatment Leads to Interferon-Dependent Clearance of Hepatitis B Virus in a Hydrodynamic Injection Mouse Model

2014 ◽  
Vol 88 (18) ◽  
pp. 10421-10431 ◽  
Author(s):  
J. Wu ◽  
S. Huang ◽  
X. Zhao ◽  
M. Chen ◽  
Y. Lin ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mouse Model ◽  
Poly I:C ◽  
Hydrodynamic Injection ◽  
B Virus

scholarly journals Persistence of Hepatitis B Virus DNA and the Tempos between Virion Secretion and Genome Maturation in a Mouse Model

2019 ◽  
Vol 93 (22) ◽  
Author(s):  
Szu-Yao Wu ◽  
Ya-Shu Chang ◽  
Tien-Hua Chu ◽  
Chiaho Shih
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mouse Model ◽  
Core Protein ◽  
Wild Type ◽  
Viral Dna ◽  
Naturally Occurring ◽  
B Virus

ABSTRACT Hepatitis B virus (HBV) core protein (HBc) accumulates frequent mutations in natural infection. Wild-type HBV is known to secrete predominantly virions containing mature DNA genome. However, a frequent naturally occurring HBc variant, I97L, changing from an isoleucine to a leucine at amino acid 97, exhibited an immature secretion phenotype in culture, which preferentially secretes virions containing immature genomes. In contrast, mutant P130T, changing from a proline to a threonine at amino acid 130, exhibited a hypermaturation phenotype by accumulating an excessive amount of intracellular fully mature DNA genome. Using a hydrodynamic delivery mouse model, we studied the in vivo behaviors of these two mutants, I97L and P130T. We detected no naked core particles in all hydrodynamically injected mice. Mutant I97L in mice exhibited pleiotropic phenotypes: (i) excessive numbers of serum HBV virions containing immature genomes, (ii) significantly reduced numbers of intracellular relaxed-circle and single-stranded DNAs, and (iii) less persistent intrahepatic and secreted HBV DNAs than wild-type HBV. These pleiotropic phenotypes were observed in both immunocompetent and immunodeficient mice. Although mutant P130T also displayed a hypermaturation phenotype in vivo, it cannot efficiently rescue the immature virion secretion of mutant I97L. Unexpectedly, the single mutant P130T exhibited in vivo a novel phenotype in prolonging the persistence of HBV genome in hepatocytes. Taken together, our studies provide a plausible rationale for HBV to regulate envelopment morphogenesis and virion secretion via genome maturity, which is likely to play an important role in the persistence of viral DNA in this mouse model. IMPORTANCE Chronic infection with human hepatitis B virus (HBV) could lead to cirrhosis and hepatoma. At present, there is no effective treatment to eradicate the virus from patients. HBV in chronic carriers does not exist as a single homogeneous population. The most frequent naturally occurring mutation in HBV core protein occurs at amino acid 97, changing an isoleucine to leucine (I97L). One dogma in the field is that only virions containing a mature genome are preferentially secreted into the medium. Here, we demonstrated that mutant I97L can secrete immature genome in mice. Although viral DNA of mutant I97L with immature genome is less persistent than wild-type HBV in time course experiments, viral DNA of mutant P130T with genome hypermaturation, surprisingly, is more persistent. Therefore, virion secretion regulated by genome maturity could influence viral persistence. It remains an open issue whether virion secretion could be a drug target for HBV therapy.

scholarly journals In Vitro Antihepadnaviral Activities of Combinations of Penciclovir, Lamivudine, and Adefovir

2000 ◽  
Vol 44 (3) ◽  
pp. 551-560 ◽  
Author(s):  
Danni Colledge ◽  
Gilda Civitico ◽  
Stephen Locarnini ◽  
Tim Shaw
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Immunomodulatory Activity ◽  
Clinical Use ◽  
Duck Hepatitis ◽  
B Virus ◽  
The Individual

ABSTRACT Penciclovir {9-[2-hydroxy-1-(hydroxymethyl)-ethoxymethyl]guanine [PCV]}, lamivudine ([−]-β-l-2′,3′-dideoxy-3′-thiacytidine [3TC]), and adefovir (9-[2-phosphonylmethoxyethyl]-adenine [PMEA]) are potent inhibitors of hepatitis B virus (HBV) replication. Lamivudine has recently received approval for clinical use against chronic human HBV infection, and both PCV and PMEA have undergone clinical trials against HBV in their respective prodrug forms {famciclovir and adefovir dipivoxil [bis-(POM)-PMEA]}. Since multidrug combinations are likely to be used to control HBV infection, investigation of potential interactions between PCV, 3TC, and PMEA is important. Primary duck hepatocyte cultures which were either acutely or congenitally infected with the duck hepatitis B virus (DHBV) were used to investigate in vitro interactions between PCV, 3TC, and PMEA. Here we show that the anti-DHBV effects of all the combinations containing PCV, 3TC, and PMEA are greater than that of each of the individual components and that their combined activities are approximately additive or synergistic. These results may underestimate the potential in vivo usefulness of PMEA-containing combinations, since there is evidence that PMEA has immunomodulatory activity and, at least in the duck model of chronic HBV infection, is capable of inhibiting DHBV replication in cells other than hepatocytes, the latter being unaffected by treatment with either PCV or 3TC. Further investigation of the antiviral activities of these drug combinations is therefore required, particularly since each of the component drugs is already in clinical use.

scholarly journals Susceptibility of Different Hepatitis B Virus Isolates to Interferon-Alpha in a Mouse Model Based on Hydrodynamic Injection

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e90977 ◽  
Author(s):  
Jingjiao Song ◽  
Yun Zhou ◽  
Sheng Li ◽  
Baoju Wang ◽  
Xin Zheng ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mouse Model ◽  
Interferon Alpha ◽  
Hydrodynamic Injection ◽  
Model Based ◽  
B Virus ◽  
Virus Isolates
Sign in / Sign up

Export Citation Format

Share Document