A multiscale mathematical model of chronic hepatitis B virus infection

Zoom Link: https://ubc.zoom.us/j/68688109781?pwd=SFFSZGF3QU9RWk9pdGl1ZHZhQ3NVUT09
Meeting ID: 686 8810 9781
Passcode: 166808

**There will be a reception (tea/coffee and snacks) in PIMS Lounge ESB 4133, before the Colloquium, starting at 12:30pm.

As the search for a cure for chronic hepatitis B virus infection continues, pharmaceutical companies have developed antivirals that target different stages of the intracellular life cycle of the virus. Earlier developed drugs such as pegylated interferon and nucleos(t)ide analogues (NAs) have shown effective viral suppression during treatment in individuals with chronic HBV infection. However, the NAs may need to be taken indefinitely to maintain viral suppression, and pegylated interferon has side effects that limit its use. The development of a new class of drugs, called capsid assembly modulators (CAMs), has created renewed hope for finding a functional cure for chronic HBV infection.  
We developed a multiscale mathematical model of chronic HBV infection that incorporates steps in the intracellular life cycle and extracellular kinetics of the virus.  
We fit our model to the longitudinal HBV RNA, HBV DNA, and alanine aminotransferase (ALT) measurements from 27 individuals with chronic HBV infection treated with a first-generation CAM, vebicorvir for 28 days. From this, we estimated the effectiveness of vebicorvir in preventing the production of encapsidation pgRNA. We also used our model to identify the biological mechanisms contributing to the different phases of viral decline observed during therapy.
Our model provides a quantitative framework for studying the intracellular and extracellular kinetics of chronic HBV infection and a conceptual framework for estimating the in vivo effectiveness of drugs that target different aspects of the intracellular life cycle of the virus.