scholarly journals In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2247
Author(s):  
Shonisani Wendy Limani ◽  
Njabulo Mnyandu ◽  
Abdullah Ely ◽  
Reubina Wadee ◽  
Anna Kramvis ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Vectors ◽  
Cultured Cells ◽  
Sub Saharan Africa ◽  
Interferon Response ◽  
Core Antigen ◽  
B Virus

The paucity of animal models that simulate the replication of the hepatitis B virus (HBV) is an impediment to advancing new anti-viral treatments. The work reported here employed recombinant adeno-associated viruses (AAVs) to model HBV subgenotype A1 and subgenotype D3 replication in vitro and in vivo. Infection with subgenotype A1 is endemic to parts of sub-Saharan Africa, and it is associated with a high risk of hepatocellular carcinoma. Recombinant AAV serotype 2 (AAV2) and 8 (AAV8) vectors bearing greater-than-genome-length sequences of HBV DNA from subgenotype A1 and D3, were produced. Transduced liver-derived cultured cells produced HBV surface antigen and core antigen. Administration of AAV8 carrying HBV subgenotype A1 genome (AAV8-A1) to mice resulted in the sustained production of HBV replication markers over a six-month period, without elevated inflammatory cytokines, expression of interferon response genes or alanine transaminase activity. Markers of replication were generally higher in animals treated with subgenotype D3 genome-bearing AAVs than in those receiving the subgenotype A1-genome-bearing vectors. To validate the use of the AAV8-A1 murine model for anti-HBV drug development, the efficacy of anti-HBV artificial primary-microRNAs was assessed. Significant silencing of HBV markers was observed over a 6-month period after administering AAVs. These data indicate that AAVs conveniently and safely recapitulate the replication of different HBV subgenotypes, and the vectors may be used to assess antivirals’ potency.

scholarly journals In Vivo Inhibition of Anti-Hepatitis B Virus Core Antigen (HBcAg) Immunoglobulin G Production by HBcAg-Specific CD4+ Th1-Type T-Cell Clones in a hu-PBL-NOD/SCID Mouse Model

2001 ◽  
Vol 75 (23) ◽  
pp. 11449-11456 ◽  
Author(s):  
Tinghua Cao ◽  
Philip Meuleman ◽  
Isabelle Desombere ◽  
Matti Sällberg ◽  
Geert Leroux-Roels
Keyword(s):  
T Cells ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Immunoglobulin G ◽  
Core Antigen ◽  
Cell Clones ◽  
B Virus

ABSTRACT Hepatitis B virus (HBV) core antigen (HBcAg)-specific CD4+ T-cell responses are believed to play an important role in the control of human HBV infection. In the present study, HBcAg-specific, HLA-DR13*-restricted CD4+ Th1-type T-cell clones were generated which secreted both gamma interferon and tumor necrosis factor alpha after in vitro antigen stimulation. These HBcAg-specific CD4+ Th1-type T cells were able to lyse HBc peptide-loaded Epstein-Barr virus-transformed lymphoblastoid target cells in vitro. To examine whether these HLA-DR13*-restricted human CD4+ Th1 T cells also display the same cytotoxic effects in vivo, we transferred peripheral blood leukocytes (PBL) derived from HBV-infected donors or an HBV-naı̈ve donor sharing the DR13*, together with the HBcAg-specific CD4+ Th1-type T cells and HBcAg, directly into the spleen of optimally conditioned Nod/LtSz-Prkdcscid/Prkdcscid (NOD/SCID) mice. The production of both secondary anti-HBc-immunoglobulin G (anti-HBc-IgG) and primary HBcAg-binding IgM in hu-PBL-NOD/SCID mice was drastically inhibited by HBcAg-specific CD4+ Th1-type T cells. No inhibition was observed when CD4+ Th1 cells and donor PBL did not share an HLA-DR13. These results suggest that HBcAg-specific CD4+ Th1 T cells may be able to lyse HBcAg-binding, or -specific, B cells that have taken up and presented HBcAg in a class II-restricted manner. Thus, HBcAg-specific CD4+ Th1-type T cells can modulate the function and exert a regulatory role in deleting HBcAg-binding, or -specific, human B cells in vivo, which may be of importance in controlling the infection.

Effect of 3′-azido-3′-deoxythymidine on replication of duck hepatitis B virus in vivo and in vitro

1989 ◽  
Vol 29 (4) ◽  
pp. 244-248 ◽  
Author(s):  
Hideaki Haritani ◽  
Toshikazu Uchida ◽  
Yasunori Okuda ◽  
Toshio Shikata
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

scholarly journals Inactivation of Hepatitis B Virus Replication in Cultured Cells and In Vivo with Engineered Transcription Activator-Like Effector Nucleases

2013 ◽  
Vol 21 (10) ◽  
pp. 1889-1897 ◽  
Author(s):  
Kristie Bloom ◽  
Abdullah Ely ◽  
Claudio Mussolino ◽  
Toni Cathomen ◽  
Patrick Arbuthnot
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Replication ◽  
Cultured Cells ◽  
Transcription Activator ◽  
B Virus

In vitro and in vivo anti-hepatitis B virus activities of the lignan nirtetralin B isolated from Phyllanthus niruri L.

2014 ◽  
Vol 157 ◽  
pp. 62-68 ◽  
Author(s):  
Sheng Liu ◽  
Wanxing Wei ◽  
Yubin Li ◽  
Xing Lin ◽  
Kaichuang Shi ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Phyllanthus Niruri ◽  
B Virus

scholarly journals Anti-Hepatitis B Virus Activity of Esculetin from Microsorium fortunei In Vitro and In Vivo

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3475 ◽  
Author(s):  
Si-Xin Huang ◽  
Jun-Fei Mou ◽  
Qin Luo ◽  
Qing-Hu Mo ◽  
Xian-Li Zhou ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Antiviral Drug ◽  
Liver Carcinoma ◽  
Dependent Manner ◽  
Duck Hepatitis ◽  
B Virus

Coumarins are widely present in a variety of plants and have a variety of pharmacological activities. In this study, we isolated a coumarin compound from Microsorium fortunei (Moore) Ching; the compound was identified as esculetin by hydrogen and carbon spectroscopy. Its anti-hepatitis B virus (HBV) activity was investigated in vitro and in vivo. In the human hepatocellular liver carcinoma 2.2.15 cell line (HepG2.2.15) transfected with HBV, esculetin effecting inhibited the expression of the HBV antigens and HBV DNA in vitro. Esculetin inhibited the expression of Hepatitis B virus X (HBx) protein in a dose-dependent manner. In the ducklings infected with duck hepatitis B virus (DHBV), the levels of DHBV DNA, duck hepatitis B surface antigen (DHBsAg), duck hepatitis B e-antigen (DHBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased significantly after esculetin treatment. Summing up the above, the results suggest that esculetin efficiently inhibits HBV replication both in vitro and in vivo, which provides an opportunity for further development of esculetin as antiviral drug.

Duck hepatitis B virus polymerase gene mutants associated with resistance to lamivudine have a decreased replication capacity in vitro and in vivo

2001 ◽  
Vol 34 (1) ◽  
pp. 114-122 ◽  
Author(s):  
Béatrice Seignères ◽  
Stéphanie Aguesse-Germon ◽  
Christian Pichoud ◽  
Isabelle Vuillermoz ◽  
Catherine Jamard ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Replication Capacity ◽  
Polymerase Gene ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

Genetic immunization against hepatitis B virus with calcium phosphate nanoparticles in vitro and in vivo

2020 ◽  
Vol 110 ◽  
pp. 254-265
Author(s):  
Leonardo Rojas-Sánchez ◽  
Ejuan Zhang ◽  
Viktoriya Sokolova ◽  
Maohua Zhong ◽  
Hu Yan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Calcium Phosphate ◽  
Hepatitis B ◽  
Genetic Immunization ◽  
B Virus ◽  
Calcium Phosphate Nanoparticles

In vitro and in vivo anti-hepatitis B virus activities of the lignan niranthin isolated from Phyllanthus niruri L.

2014 ◽  
Vol 155 (2) ◽  
pp. 1061-1067 ◽  
Author(s):  
Sheng Liu ◽  
Wanxing Wei ◽  
Kaichuang Shi ◽  
Xun Cao ◽  
Min Zhou ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Phyllanthus Niruri ◽  
B Virus

scholarly journals Interaction between ganciclovir and foscarnet as inhibitors of duck hepatitis B virus replication in vitro.

1996 ◽  
Vol 40 (5) ◽  
pp. 1180-1185 ◽  
Author(s):  
G Civitico ◽  
T Shaw ◽  
S Locarnini
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Duck Hepatitis ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Dose Limiting Toxicity

Safe and effective treatments for chronic hepatitis B virus (HBV) infection have yet to be developed. Both ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) and foscarnet (trisodium phosphonoformate hexahydrate) are potent inhibitors of hepadnavirus replication when used individually in vitro and in vivo. However, the clinical usefulness of each drug is reduced by dose-limiting toxicity, especially during long-term monotherapy. Here we demonstrate additive inhibition of duck HBV DNA replication in cultures of primary duck hepatocytes congenitally infected with duck HBV by combinations of ganciclovir and foscarnet at low, clinically achievable concentrations. These results suggest that the effects of ganciclovir and foscarnet against HBV may be additive in vivo.

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