Pregenomic RNA: How to assist the management of chronic hepatitis B?

Wu, Yongbin; Wen, Jian Guo; Xiao, Weiwei; Bao, Zhenan

doi:10.1002/rmv.2051

Cited by 17 publications

(12 citation statements)

References 91 publications

(117 reference statements)

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“…Five viral mRNAs are produced ( Figure 2 ), including the pregenomic RNA (pgRNA), which is the main intermediate in the viral replication. pgRNA is exported to the cytosol where its 5′-end binds to the HBVPol and induces the packaging process [ 4 , 18 ]. Then, inside the nucleocapsid, the pgRNA is reverse transcribed by the viral polymerase into a new-rcDNA.…”

Section: Hbv Replicative Cyclementioning

confidence: 99%

“…Then, inside the nucleocapsid, the pgRNA is reverse transcribed by the viral polymerase into a new-rcDNA. Alternatively, a double-strand linear DNA (dslDNA) is formed and plays an important role in the HBV-DNA integration into the host genome [ 4 , 18 ]. The mature capsids can either deliver the rcDNA into the nucleus, increasing the cccDNA content or binding to HBV surface proteins in the endoplasmic reticulum (ER) to be secreted as virions outside the hepatocytes [ 16 ].…”

Section: Hbv Replicative Cyclementioning

confidence: 99%

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Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability

Campos-Valdez

Monroy-Ramírez

Armendáriz‐Borunda

et al. 2021

Viruses

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The immunopathogenesis and molecular mechanisms involved during a hepatitis B virus (HBV) infection have made the approaches for research complex, especially concerning the patients’ responses in the course of the early acute stage. The study of molecular bases involved in the viral clearance or persistence of the infection is complicated due to the difficulty to detect patients at the most adequate points of the disease, especially in the time lapse between the onset of the infection and the viral emergence. Despite this, there is valuable data obtained from animal and in vitro models, which have helped to clarify some aspects of the early immune response against HBV infection. The diversity of the HBV (genotypes and variants) has been proven to be associated not only with the development and outcome of the disease but also with the response to treatments. That is why factors involved in the virus evolution need to be considered while studying hepatitis B infection. This review brings together some of the published data to try to explain the immunological and molecular mechanisms involved in the different stages of the infection, clinical outcomes, viral persistence, and the impact of the variants of HBV in these processes.

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Section: Hbv Replicative Cyclementioning

confidence: 99%

Section: Hbv Replicative Cyclementioning

confidence: 99%

Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability

Campos-Valdez

Monroy-Ramírez

Armendáriz‐Borunda

et al. 2021

Viruses

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“…HBV pregenomic RNA (pgRNA) is an intermediate of HBV replication (14). In recent years, many researchers have confirmed that the HBV pgRNA in serum is derived from the active transcription of HBV cccDNA in the infected hepatocytes (15)(16)(17). In particular, the serum HBV RNA level in patients receiving nucleoside(t)ide analog (NA) treatment can reflect the presence of the cccDNA and its transcriptional activity in hepatocytes, when the reverse transcription and DNA synthesis of the virus are inhibited (8,18).…”

mentioning

confidence: 99%

Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes

Lin

et al. 2020

J Clin Microbiol

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Pregenomic RNA (pgRNA) is a direct transcription product of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and it plays important roles in viral genome amplification and replication. This study was designed to investigate whether serum pgRNA is a strong alternative marker for reflecting HBV cccDNA levels and to analyze the correlation between serum pgRNA, serum HBV DNA, and hepatitis B surface antigen (HBsAg). A total of 400 HBV-infected patients who received nucleos(t)ide analog (NA) therapy with different clinical outcomes were involved in this research. Case groups included asymptomatic hepatitis B virus carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) patients, with 100 patients in each group. The results showed that the levels of HBV pgRNA had significant differences between these 4 groups. Serum pgRNA levels correlated well with serum HBV DNA and HBsAg levels (HBV pgRNA levels versus HBV DNA levels, r = 0.58, P < 0.001; HBV pgRNA levels versus HBsAg levels, r = 0.47, P < 0.001). In addition, we focused on the 108 HBV-infected patients with HBV DNA levels of <500 IU/ml; it was surprising to find that in 17.57% (13/74) of cases, HBV pgRNA could be detected even when the HBV DNA level was below 20 IU/ml. In conclusion, HBV pgRNA levels in serum can be a surrogate marker for intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg. The detection of serum HBV pgRNA levels may provide a reference for clinical monitoring of cccDNA levels and the selection of appropriate timing for discontinuing antiviral therapy, especially when HBV DNA levels are below the detection limit.

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“…We monitored the dynamic change of serum pgRNA during the long-term NAs therapy, and found that serum pgRNA in most patients, generally speaking, showed a decreasing trend from baseline to 96 months after treatment, which was contrast with the earlier results that serum pgRNA increased both in CHB patients ( 10 ) and in HBV transgenic mice with NAs therapy ( 9 ). The reason may be that NAs can block the HBV polymerase-mediated synthesis of rcDNA from the pgRNA template, resulting in the excessive accumulation of encapsidated pgRNA during a short treatment period ( 17 ). However, along with the time of treatment, NAs might eventually, to some extent, reduce the replenishment of cccDNA pool via the suppression of rcDNA, thereby inhibiting the generation of HBV RNA virions.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy

et al. 2022

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BackgroundTissue covalently closed circular DNA (cccDNA) can reflect the activity of HBV replication. However, it is impractical to assess intrahepatic cccDNA in every outpatient. Serum pregenome RNA (pgRNA) is transcribed from intrahepatic cccDNA and may reflect the activity of intrahepatic cccDNA. We explored the dynamics and the potential role of serum pgRNA in patients receiving long-term NAs treatment.MethodsSerum pgRNA, HBV DNA, HBsAg, HBeAg, and ALT levels were quantified, and the relationships between serum pgRNA and these common clinical indicators before and after the treatment were investigated.ResultsSerum pgRNA showed dynamic change during the 96-month NAs therapy, and serum pgRNA levels were positive and detectable in 19 patients with undetectable serum HBV DNA. Serum pgRNA showed strong and positive correlation with serum HBV DNA (r = 0.693, p < 0.001) and serum HBsAg levels (r = 0.621, p < 0.001) at baseline. Patients with HBeAg seroconversion had lower baseline serum pgRNA levels (p = 0.002). The area under the curve (AUC) of baseline serum pgRNA for predicting HBeAg seroconversion was 0.742 (95% CI: 0.606–0.850) with 63.16% sensitivity and 80.56% specificity. The cumulative HBeAg seroconversion rate was higher in patients with low serum pgRNA (p = 0.001).ConclusionSerum pgRNA of low level at baseline or great decline at month 6 may independently predict the high incidence of undetectable serum pgRNA at year 4 following NAs therapy, and the baseline serum pgRNA may serve as a novel predictor for HBeAg seroconversion during NAs therapy.

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Pregenomic RNA: How to assist the management of chronic hepatitis B?

Cited by 17 publications

References 91 publications

Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability

Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability

Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes

Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy

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