title: Modeling the effects of covalently closed circular DNA and dendritic cells in chronic HBV infection.
abstract: The contribution of covalently closed circular DNA (cccDNA) and dendritic cells (DCs) to the progression of chronic hepatitis B virus (HBV) infection remains largely unknown. A dynamic model with seven cell types was proposed based on the biological mechanisms of viral replication and the host immune response. The cccDNA self-amplification rate was found to be closely related to both the basic reproduction number of the virus and the immune response. The combination of the cccDNA self-amplification rate and the initial activated DC count induces rich dynamics. Applying our model to the clinical data of untreated patients, we found that chronic patients have a high cccDNA self-amplification rate. For antiviral treatment, an overall drug effectiveness was introduced and the critical drug effectiveness was obtained. The model predicts that timely long-term therapy is needed to reduce the symptoms of HBV and to maintain the benefits of treatment.
authors.affiliation: School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China; Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Furong
authors.initials: F
authors.lastname: Lu
authors.affiliation: Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: gh_deng@hotmail.com.
authors.forename: Guohong
authors.initials: G
authors.lastname: Deng
authors.affiliation: School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. Electronic address: kfwang001@gmail.com.
authors.forename: Kaifa
authors.initials: K
authors.lastname: Wang
mesh_terms: D004270:DNA, Circular / Q000276:immunology*; D004279:DNA, Viral / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D018448:Models, Immunological; D014779:Virus Replication / Q000276:immunology*
chemical_list: D004270:DNA, Circular; D004279:DNA, Viral
keywords: Antiviral therapy; Dynamic model; Hepatitis B virus; Overall drug effectiveness; cccDNA self-amplification rate