title: Dynamics of in vivo hepatitis D virus infection.
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.
  
  
  
  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.
authors.affiliation: School of Mathematics and Statistics, University of New South Wales, NSW 2052, Sydney, Australia. Electronic address: ashish.goyal@student.unsw.edu.au.
authors.forename: Ashish
authors.initials: A
authors.lastname: Goyal
authors.affiliation: School of Mathematics and Statistics, University of New South Wales, NSW 2052, Sydney, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Murray
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D060085:Coinfection; D003198:Computer Simulation; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects; D003699:Hepatitis D / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D003698:Hepatitis Delta Virus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D017368:Protein Prenylation
chemical_list: D000998:Antiviral Agents
keywords: Hepatitis-B virus; Interferon; Mathematical model; Pathogenesis; Prenylation