Enhanced hepatitis B virus (HBV) pre-genomic RNA levels and higher transcription efficiency of defective HBV genomes

Kandpal, Manish; Samal, Jasmine; Biswas, Banhi; Negi, Avinash; Mishra, Vikash Chandra; Tyagi, Neetu; Vimarsh, Raina; Vivekanandan, Perumal

doi:10.1099/jgv.0.000256

Cited by 9 publications

(12 citation statements)

References 30 publications

(34 reference statements)

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“…Cell culture studies suggested that HBSP promotes hepatoma cell proliferation and migration [136]. Alternatively, pathogenicity of the splicing variant could be attributed to increased expression of core and HBx proteins as well as DNA replication [133, 137], as a consequence of the large deletion which prevents the transcription of 2.4-kb and 2.1-kb RNAs.…”

Section: Mutations Selected At the Immune Clearance Phase Of Chronmentioning

confidence: 99%

Overview of hepatitis B viral replication and genetic variability

Tong

Revill

2016

Journal of Hepatology

325

318

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Summary Chronic infection with hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). HBV isolates worldwide can be divided into 10 genotypes. Moreover, the immune clearance phase selects for mutations in different parts of the viral genome. The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype and adaptive mutations, as well as environmental factors. Core promoter mutations and mutations abolishing HBeAg expression have been implicated in acute liver failure, while genotypes B, C, subgenotype A1, core promoter mutations, preS deletions, C-terminal truncation of envelope proteins, and spliced pregenomic RNA are associated with HCC development. Our efforts to treat and prevent HBV infection are hampered by the emergence of drug resistant mutants and vaccine escape mutants. This paper provides an overview of the HBV life cycle, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance.

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Section: Mutations Selected At the Immune Clearance Phase Of Chronmentioning

confidence: 99%

Overview of hepatitis B viral replication and genetic variability

Tong

Revill

2016

Journal of Hepatology

325

318

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“…The current study compared serum HBV RNA levels between patients with HBeAg-positive and -negative CHB 4 Hepat Mon. In Press(In Press):e62079.…”

Section: Comparison Between Patients With Hbeag-positive Andnegative mentioning

confidence: 99%

“…Theoretically, any host or viral factors that increase the production of pgRNA or block the reverse transcription of pgRNA in relaxed circular DNA may cause excess of pgRNA. Accumulating evidences suggest that excess pgRNA might present in virion-like particles and represent the majority of detectable HBV RNA in sera (3) and supernatant of HBV cell cultures (4,5).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

et al. 2018

Hepat Mon

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Background: The serum hepatitis B virus (HBV) RNA is suggested as a potential new biomarker of HBV infection. However, it is not fully understood. Objectives: The current study aimed at characterizing serum HBV RNA in patients with untreated chronic hepatitis B (CHB) and genotype B and C HBV infection. Methods: A large cohort of 483 patients with hepatitis B e antigen (HBeAg)-positive and -negative was performed. The routine serum biomarkers of HBV infection were tested. HBV genotyping was carried out by direct sequencing. Serum HBV RNA levels were quantified using a method described in the authors' previous study (lower limit of detection: 66.7 IU/mL). Results: Serum HBV RNA was detected in 92.5% (394/426) of the patients with HBeAg-positive and 31.6% (18/57) of HBeAg-negative ones; a positive association was observed between HBeAg and HBV RNA statuses in the subjects. Alanine aminotransferase (ALT), HBV DNA, and genotype were the independent predictors in patients with HBeAg-positive CHB (P = 0.024, 0.001 and 0.014, respectively), while it was HBV DNA in the negative ones (P = 0.000) for serum HBV RNA detectability. Serum HBV RNA was positively correlated with ALT, aspartate transaminase (AST) and HBV DNA, regardless of HBeAg status, and with hepatitis B surface antigen (HBsAg) in HBeAg-positive ones (P < 0.05). Conclusions: Serum HBV RNA may be affected by HBeAg status, serum HBV DNA, HBsAg levels, HBV genotype, ALT, and AST levels. There might be some similarities between the characteristics of serum HBV RNA, and serum HBV DNA and HBsAg, regardless of its distinctive features. The roles of serum HBV RNA in viral replication, infection, survival, disease progression, and antiviral responses need to be investigated in further studied.

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“…HBV encoded proteins may regulate each other or HBV replication 28 – 31 . We therefore wanted to test if the inhibition of HBsAg is independent of inhibition of other HBV encoded proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Secreted and intracellular HBsAg levels were estimated using MONOLISA HBsAg Ultra ELISA kit (BioRad) as described earlier 23 , 28 . Cells transfected with HBV construct and treated with DMSO (0.5% final concentration) were used as controls.…”

Section: Methodsmentioning

confidence: 99%

A novel piperazine derivative that targets hepatitis B surface antigen effectively inhibits tenofovir resistant hepatitis B virus

Kiruthika

Bhat

Dash

et al. 2021

Sci Rep

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Chronic hepatitis B virus (HBV) infection is a global problem. The loss of hepatitis B surface antigen (HBsAg) in serum is a therapeutic end point. Prolonged therapy with nucleoside/nucleotide analogues targeting the HBV-polymerase may lead to resistance and rarely results in the loss of HBsAg. Therefore, inhibitors targeting HBsAg may have potential therapeutic applications. Here, we used computational virtual screening, docking, and molecular dynamics simulations to identify potential small molecule inhibitors against HBsAg. After screening a million molecules from ZINC database, we identified small molecules with potential anti-HBV activity. Subsequently, cytotoxicity profiles and anti-HBV activities of these small molecules were tested using a widely used cell culture model for HBV. We identified a small molecule (ZINC20451377) which binds to HBsAg with high affinity, with a KD of 65.3 nM, as determined by Surface Plasmon Resonance spectroscopy. Notably, the small molecule inhibited HBsAg production and hepatitis B virion secretion (10 μM) at low micromolar concentrations and was also efficacious against a HBV quadruple mutant (CYEI mutant) resistant to tenofovir. We conclude that this small molecule exhibits strong anti-HBV properties and merits further testing.

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Enhanced hepatitis B virus (HBV) pre-genomic RNA levels and higher transcription efficiency of defective HBV genomes

Cited by 9 publications

References 30 publications

Overview of hepatitis B viral replication and genetic variability

Overview of hepatitis B viral replication and genetic variability

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

A novel piperazine derivative that targets hepatitis B surface antigen effectively inhibits tenofovir resistant hepatitis B virus

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