In vitro cell culture models to study hepatitis B and D virus infection

Guo, Hongbo; Urban, Stephan; Wang, Wenshi

doi:10.3389/fmicb.2023.1169770

Cited by 6 publications

(3 citation statements)

References 67 publications

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“…Transcription of HBV pgRNA and viral genome replication can be controlled by tetracycline in HepAD38 cells. Compared with HepG2.2.15 cell line, HepAD38 cell line could be regulated, and HBV virus production and intracellular cccDNA accumulation in Tet‐off condition were significantly higher than those in HepG2.2.15 cell line 36 …”

Section: Resultsmentioning

confidence: 91%

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

Zhang,

Yuan,

Wang

et al. 2024

Journal of Medical Virology

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Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti‐HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion‐related molecules on HBV replication. The in‐depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA‐histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA‐dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. These data suggest that TRPV4 exerts multifaceted HBV‐related synergistic factors and may serve as a therapeutic target for CHB.

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Section: Resultsmentioning

confidence: 91%

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

Zhang,

Yuan,

Wang

et al. 2024

Journal of Medical Virology

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“…[23] Some animals are natural hosts of other hepadnaviruses that are closely related to HBV and have been used as experimental models for many years, such as the woodchuck (infected with woodchuck hepatitis virus) and duck (infected with duck HBV). [24] Although the mouse is the best characterized and most convenient laboratory animal, it cannot be infected with HBV. mNTCP could not facilitate HBV entry.…”

Section: Discussionmentioning

confidence: 99%

Limited disassembly of cytoplasmic hepatitis B virus nucleocapsids restricts viral infection in murine hepatic cells

et al. 2022

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Background and Aims: Murine hepatic cells cannot support hepatitis B virus (HBV) infection even with supplemental expression of viral receptor, human sodium taurocholate cotransporting polypeptide (hNTCP). However, the specific restricted step remains elusive. In this study, we aimed to dissect HBV infection process in murine hepatic cells. Approach and Results: Cells expressing hNTCP were inoculated with HBV or hepatitis delta virus (HDV). HBV pregenomic RNA (pgRNA), covalently closed circular DNA (cccDNA), and different relaxed circular DNA (rcDNA) intermediates were produced in vitro. The repair process from rcDNA to cccDNA was assayed by in vitro repair experiments and in mouse with hydrodynamic injection. Southern blotting and in situ hybridization were used to detect HBV DNA. HBV, but not its satellite virus HDV, was restricted from productive infection in murine hepatic cells expressing hNTCP. Transfection of HBV pgRNA could establish HBV replication in human, but not in murine, hepatic cells. HBV replication‐competent plasmid, cccDNA, and recombinant cccDNA could support HBV transcription in murine hepatic cells. Different rcDNA intermediates could be repaired to form cccDNA both in vitro and in vivo. In addition, rcDNA could be detected in the nucleus of murine hepatic cells, but cccDNA could not be formed. Interestingly, nuclease sensitivity assay showed that the protein‐linked rcDNA isolated from cytoplasm was completely nuclease resistant in murine, but not in human, hepatic cells. Conclusions: Our results imply that the disassembly of cytoplasmic HBV nucleocapsids is restricted in murine hepatic cells. Overcoming this limitation may help to establish an HBV infection mouse model.

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“…DHBV was initially identified from Pekin ducks in China ( 16 ) and later identified in different geographical areas including the United States ( 16 ), Australia ( 17 , 18 ), Germany ( 19 ), and South Africa ( 20 ). In terms of genetic organization, virus replication, and biological characteristics, DHBV is like HBV ( 21 ). However, breeding ducks may experience a persistent infection of DHBV, which can cause significant damage to duck hatching and growth ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic diversity and phylogeographic dynamics of avihepadnavirus: a comprehensive full-length genomic view

Sikandar,

Shah,

Xing

2024

Front. Vet. Sci.

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Avihepadnavirus is a genus of the Hepadnaviridae family. It primarily infects birds, including species of duck, geese, cranes, storks, and herons etc. To understand the genetic relatedness and evolutionary diversity among avihepadnavirus strains, a comprehensive analysis of the available 136 full-length viral genomes (n = 136) was conducted. The genomes were classified into two major genotypes, i.e., GI and GII. GI viruses were further classified into 8 sub-genotypes including DHBV-I (duck hepatitis B virus-I), DHBV-II (Snow goose Hepatitis B, SGHBV), DHBV-III, RGHBV (rossgoose hepatitis B virus), CHBV (crane hepatitis B virus), THBV (Tinamou hepatitis B virus), STHBV (stork hepatitis B virus), and HHBV (Heron hepatitis B virus). DHBV-I contains two sub-clades DHBV-Ia and DHBV-Ib. Parrot hepatitis B virus (PHBV) stains fall into GII which appeared as a separate phylogenetic branch/clade. All the subtypes of viruses in GI and GII seem to be genetically connected with viruses of DHBV-I by multiple mutational steps in phylogeographic analysis. Furthermore, 16 potential recombination events among different sub-genotypes in GI and one in GII were identified, but none of which is inter-genotypic between GI and GII. Overall, the results provide a whole picture of the genetic relatedness of avihepadnavirus strains, which may assist in the surveillance of virus spreading.

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In vitro cell culture models to study hepatitis B and D virus infection

Cited by 6 publications

References 67 publications

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin

Limited disassembly of cytoplasmic hepatitis B virus nucleocapsids restricts viral infection in murine hepatic cells

Genetic diversity and phylogeographic dynamics of avihepadnavirus: a comprehensive full-length genomic view

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