Dynamics of in vivo hepatitis D virus infection. (7th June 2016)

• Record Type: Journal Article
• Authors: Goyal, Ashish; Murray, John M.
• Is Part Of: Journal of theoretical biology. Volume 398(2016)
• Page Start: 9
• Page End: 19
• Publication Date: 2016-06-07
• Subjects: HDV Hepatitis D virus -- HBsAg hepatitis B Surface Antigen -- HBV Hepatitis B virus -- HCC hepatocellular carcinoma -- IFN pegylated interferon -- cccDNA covalently closed circular DNA -- pgRNA pregenomic RNA -- rcDNA double-stranded DNA-containing capsids -- AG-RNA anti-genomic RNA -- S-HDAg small delta antigen -- L-HDAg large delta antigen -- RNP ribonucleoprotein complex; Pathogenesis -- Hepatitis-B virus -- Interferon -- Prenylation -- Mathematical model; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2016.03.018
• Languages: English
• ISSNs: 0022-5193

Abstract

Abstract: Hepatitis-D virus (HDV) is a satellite virus of hepatitis-B virus (HBV) whose intracellular products are required for the completion of the HDV life cycle. HDV can replicate in a cell without the presence of HBV but needs hepatitis B surface antigen (HBsAg) to complete virus assembly and packaging. In order to better understand HDV dynamics, we developed a mathematical model and successfully simulated HBV and HDV data under a range of scenarios. Compared to HBV mono-infection, dual HDV infection resulted in lower chronic HBV DNA levels, with more marked suppression for coinfection (1 logs HBV DNA copies/ml lower) compared to superinfection (0.6 logs HBV DNA copies/ml). Although they have no effect on HBV, prenylation inhibitors may provide the best therapy for reducing HDV viremia irrespective of the stage in which they are commenced. We found that highly effective long term pegylated interferon (IFN) therapy (99.99%) eliminates HBV and HDV viremia while less effective long term IFN therapy (99%) will only produce approximately 2.03 logs and no decrease in HBV and HDV viremia respectively in both coinfection and superinfection settings. Our study also suggests that there is a substantial difference in the outcome of therapies depending upon the time of commencement. Conclusion: Mathematical modeling of HDV infection can describe the complex interplay between this virus and HBV. Simulations suggest that HDV impacts on the feedback mechanisms that maintain cccDNA levels and that targeting these mechanisms may result in new therapeutic agents for both viruses. Highlights: HDV inhibits the feedback mechanism of HBV infection. Lower cccDNA accumulation is observed during HDV superinfection than coinfection. Prenylation can serve as an effective therapy for HDV infection. Long term high efficacy interferon therapy is essential to eradicate HBV and HDV.