Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound

Wang, Jie; Shen, Tao; Huang, Xiangbo; Kumar, G. Renuka; Chen, Xiangmei; Zeng, Zhenzhen; Zhang, Ruiyang; Chen, Ran; Li, Tong; Zhang, Tianying; Yuan, Quan; Li, Pao-Chen; Huang, Qi; Colonno, Richard J.; Jia, Ji-dong; Hou, Jinlin; McCrae, Malcolm A.; Gao, Zhiliang; Ren, Hong; Xia, Ningshao; Zhang, Hui; Lu, Fengmin

doi:10.1016/j.jhep.2016.05.029

Cited by 345 publications

(505 citation statements)

References 38 publications

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“…HBV RNA can be released into the serum in the form of enveloped pregenomic RNA containing virions, 236 but the full characterisation of these circulating RNAs is ongoing. Because of its strong correlation with intrahepatic cccDNA, serum HBV RNA is an interesting marker to study cccDNA transcriptional activity.…”

Section: New Biomarkers Of Hbv Infectionmentioning

confidence: 99%

“…Because of its strong correlation with intrahepatic cccDNA, serum HBV RNA is an interesting marker to study cccDNA transcriptional activity. [236][237][238] A strong correlation between quantitative serum HBV RNA dynamics and HBeAg loss in both NA and PegIFNa treated patients 239 was recently demonstrated by using a new rapid amplification of cDNA-ends with polymerase chain reaction (RACE-PCR). 240 HBV RNA quantification might be also helpful in predicting viral rebound after discontinuation of NAs.…”

Section: New Biomarkers Of Hbv Infectionmentioning

confidence: 99%

“…240 HBV RNA quantification might be also helpful in predicting viral rebound after discontinuation of NAs. 236 It should be further explored whether the simultaneous testing of different replicative, transcriptional and translational HBV biomarkers will allow for a better definition of the individual ''activity" of the chronic HBV infection helping to better predict long-term treatment outcomes.…”

Section: New Biomarkers Of Hbv Infectionmentioning

confidence: 99%

See 2 more Smart Citations

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

3,745

2,664

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Section: New Biomarkers Of Hbv Infectionmentioning

confidence: 99%

Section: New Biomarkers Of Hbv Infectionmentioning

confidence: 99%

Section: New Biomarkers Of Hbv Infectionmentioning

confidence: 99%

See 1 more Smart Citation

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

3,745

2,664

View full text Add to dashboard Cite

“…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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“…The capsid-containing rcDNA either can reshuttle to the nucleus to replenish covalently closed circular DNA (cccDNA) or can be enveloped to form infectious viral particles that are released from the cell (8)(9)(10). In addition to the release of rcDNA-containing viral particles, it was reported that RNA-containing HBVlike particles are secreted in the cell culture supernatant and patient serum, and the release of such particles has been linked to efficacy and the prognosis of chronic hepatitis B treatment (11,12).…”

mentioning

confidence: 99%

Capsid Assembly Modulators Have a Dual Mechanism of Action in Primary Human Hepatocytes Infected with Hepatitis B Virus

Berke

Dehertogh

Vergauwen

et al. 2017

Antimicrob Agents Chemother

113

125

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Hepatitis B virus (HBV) capsid assembly is a critical step in the propagation of the virus and is mediated by the core protein. Due to its multiple functions in the viral life cycle, core became an attractive target for new antiviral therapies. Capsid assembly modulators (CAMs) accelerate the kinetics of capsid assembly and prevent encapsidation of the polymerase-pregenomic RNA (Pol-pgRNA) complex, thereby blocking viral replication. CAM JNJ-632 is a novel and potent inhibitor of HBV replication in vitro across genotypes A to D. It induces the formation of morphologically intact viral capsids, as demonstrated by size exclusion chromatography and electron microscopy studies. Antiviral profiling in primary human hepatocytes revealed that CAMs prevented formation of covalently closed circular DNA in a dosedependent fashion when the compound was added together with the viral inoculum, whereas nucleos(t)ide analogues (NAs) did not. This protective effect translated into a dose-dependent reduction of intracellular HBV RNA levels as well as reduced HBe/cAg and HBsAg levels in the cell culture supernatant. The same observation was made with another CAM (BAY41-4109), suggesting that mechanistic rather than compound-specific effects play a role. Our data show that CAMs have a dual mechanism of action, inhibiting early and late steps of the viral life cycle. These effects clearly differentiate CAMs from NAs and may translate into higher functional cure rates in a clinical setting when given alone or in combination with the current standard of care.

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Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound

Cited by 345 publications

References 38 publications

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

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

Capsid Assembly Modulators Have a Dual Mechanism of Action in Primary Human Hepatocytes Infected with Hepatitis B Virus

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