Evidence map›Paper›PMID 33079954›Full record

ArticlePLoS pathogens2020

Biogenesis and molecular characteristics of serum hepatitis B virus RNA.

Sheng Shen, Zhanglian Xie, Dawei Cai, Xiaoyang Yu, Hu Zhang, Elena S Kim, Bin Zhou, Jinlin Hou, Xiaoyong Zhang, Qi Huang and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Hepatitis B Virus Nucleocapsid Assembly.Journal of molecular biology · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Hepatitis B virus entry, assembly, and egress.Microbiology and molecular biology reviews : MMBR · 2024
    Review
  17. Article
  18. Elevated Hepatitis B virus RNA levels in hepatocellular carcinoma patients compared to cirrhotic individuals: A propensity score matched analysis.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2024
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Sheng ShenDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Zhanglian XieDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Dawei CaiAssembly Biosciences, Inc., South San Francisco, CA, United States of America.
Xiaoyang YuDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Hu ZhangDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.ORCID 0000-0002-7447-8360
Elena S KimDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.ORCID 0000-0002-8666-5681
Bin ZhouDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jinlin HouDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Xiaoyong ZhangDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.ORCID 0000-0002-6930-9423
Qi HuangAssembly Biosciences, Inc., South San Francisco, CA, United States of America.
Jian SunDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Haitao GuoDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.ORCID 0000-0002-7146-916X
Nanfang Hospital · CNUniversity of Pittsburgh · USAssembly Biosciences (United States) · US

Funding

Molecular Mechanisms of HBV cccDNA FormationR01AI110762 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GUO, HAITAO · 2016 to 2025
$3.5M
The Role of HBeAg in HBV PersistenceR01AI134818 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Haitao Guo · 2018 to 2026
$2.7M
Epigenetic Regulation of HBV cccDNA TranscriptionR01AI150255 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GUO, HAITAO · 2020 to 2024
$2.0M
Development of an HTS Assay for Discovery of HBV cccDNA InhibitorsR01AI123271 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GUO, HAITAO · 2017 to 2019
$1.2M
NIAID NIH HHS R01 AI110762NIAID NIH HHS R01 AI123271NIAID NIH HHS R01 AI134818NIAID NIH HHS R01 AI150255
6 · The paper itself

Abstract

HBV is an enveloped DNA virus that replicates its DNA genome via reverse transcription of a pregenomic (pg) RNA intermediate in hepatocytes. Interestingly, HBV RNA can be detected in virus-like particles in chronic hepatitis B (CHB) patient serum and has been utilized as a biomarker for intrahepatic cccDNA activity in treated patients. However, the biogenesis and molecular characteristics of serum HBV RNA remain to be fully defined. In this study, we found that the encapsidated serum HBV RNA predominately consists of pgRNA, which are detergent- and ribonuclease-resistant. Through blocking HBV DNA replication without affecting pgRNA encapsidation by using the priming-defective HBV mutant Y63D or 3TC treatment, we demonstrated that the cell culture supernatant contains a large amount of pgRNA-containing nonenveloped capsids and a minor population of pgRNA-containing virions. The formation of pgRNA-virion requires both capsid assembly and viral envelope proteins, which can be inhibited by capsid assembly modulators and an envelope-knockout mutant, respectively. Furthermore, the pgRNA-virion utilizes the multivesicular body pathway for egress, in a similar way as DNA-virion morphogenesis. Northern blotting, RT-PCR, and 3' RACE assays revealed that serum/supernatant HBV pgRNA are mainly spliced and devoid of the 3'-terminal sequences. Furthermore, pgRNA-virion collected from cells treated with a reversible HBV priming inhibitor L-FMAU was unable to establish infection in HepG2-NTCP cells. In summary, serum HBV RNA is secreted in noninfectious virion-like particle as spliced and poly(A)-free pgRNA. Our study will shed light on the molecular biology of serum HBV RNA in HBV life cycle, and aid the development of serum HBV RNA as a novel biomarker for CHB diagnosis and treatment prognosis.

Indexed as

CapsidCapsid ProteinsDNA, ViralHepatitis B virusHepatocytesHumansReverse TranscriptionRNA, ViralVirus AssemblyVirus ReplicationCapsid ProteinsDNA, ViralRNA, Viral

Identifiers

PMID33079954
PMCPMC7575114
OpenAlexW3094491901

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.