For proof-of-concept, known “epigenetic” compounds, which act as transcription inhibitors, have shown that cccDNA can be silenced. By reducing histone acetylation, click here the cccDNA becomes too compact to allow transcription. This approach mimics, partly, therapy with interferon. This research is still at an early stage. Due to time constraints, the next

two speakers were asked to present brief summaries. John Morrey (Utah State University, UT, USA) described four mouse models but all stages of the life cycle of HBV can be studied only in the chimeric mouse model, in which human hepatocytes are used. However, this model lacks the potential to study the immune system and it is very expensive. Stephan Menne (Georgetown University, DC, USA) described the woodchuck model. Woodchuck hepatitis virus (WHV) resembles the human virus and the disease in animals has many similarities to that in humans. Neonatal infection

becomes chronic in about 60–75% of cases. These chronic cases have virtually a 100% life-time risk of developing cancer, the time scale being about 1 year of chronic infection, followed by cancer at years 3 to 4. The use of microbicides is an active area of research for the prevention of transmission of HIV. David Katz (Duke University, NC, USA) described how mathematical models may aid drug product design. For example, if it is assumed that the microbicide gel is 400 microns thick, the epithelium selleck kinase inhibitor is 200 microns and the stroma (connective tissue) is 3000 microns and if the partition coefficient between gel and epithelium in known, then it is possible

to model drug transfer and suggest how various other parameters, for example the size of the subject, may modify drug delivery. It is important that different disciplines work together, for example biophysicists with behavioral scientists. Biophysics can help an understanding of complex physical phenomena Exoribonuclease but human behavior can be both complex and highly variable. Ralph Baric (University of North Carolina, NC, USA) noted that a particular infective agent, for example norovirus (NoV), may cause subclinical or serious disease in different individuals. In general, animal models are designed to give consistent outcomes rather than aiming to mimic the genetic diversity found in human subjects. In a collaborative effort, mice from 8 “founder” strains, including 3 wild-derived strains, were selected. The 5 founder laboratory strains were all derived ultimately from a single female mouse ca 1900. The susceptibility of the 8 founder strains to severe acute respiratory syndrome coronavirus (SARS-CoV) differed widely (LD50⩾106–102). The founder strains were cross-bred. Although ca 90% of the genes was equally distributed among the new mouse lines, there were gene combinations not seen previously.