Divergent preS Sequences in Virion-Associated Hepatitis B Virus Genomes and Subviral HBV Surface Antigen Particles From HBV e Antigen-Negative Patients.
J Infect Dis
; 218(1): 114-123, 2018 06 05.
Article
em En
| MEDLINE
| ID: mdl-29528436
ABSTRACT
Background:
Hepatitis B virus (HBV) surface proteins (HBsAg) coat the viral particle and form subviral particles (SVPs). Loss of HBsAg represents a functional cure and is an important treatment goal.Methods:
We analyzed the impact of the HBV genotypes A-E and pre-S mutations on SVP expression in hepatitis B virus e antigen (HBeAg)-negative chronic HBV-infected patients. A HBV genome harboring a preS1-deletion was analyzed in hepatoma cells.Results:
We observed a genotype-specific ratio of the 3 surface proteins (SHBs/MHBs/LHBs), reflecting differences in the morphology and composition of SVPs. Deletions/mutations in the preS1/preS2 domain, detected in released viral genomes, did not affect the molecular weight of MHBs and LHBs in these patients. In contrast, LHB molecular weight was altered in vitro using an HBV genome harboring a preS1-deletion derived from one of these patients.Conclusion:
Differences in composition of SVPs may result in genotype-specific immunogenicity and pathogenesis. In the patients with preS-mutations, secreted HBsAg and released viral genomes cannot be derived from the same genetic source. As viral genomes are derived from covalently closed circular DNA (cccDNA), HBsAg is presumably derived from integrated DNA. This important HBsAg source should be considered for novel antiviral strategies in HBeAg-negative chronic HBV-infected patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírion
/
DNA Viral
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Vírus da Hepatite B
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Hepatite B Crônica
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Antígenos de Superfície da Hepatite B
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Female
/
Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha