1. Recovery from transient hepatitis B virus infections
Supervised by Associate Professor Allison Jilbert
This study is being performed in collaboration with Dr William Mason and Dr Robert Lanford.
Exposure to HBV can lead to transient or chronic infection. Transient infections often involve widespread infection of the liver followed by recovery from infection and immunity to re-infection. The project aims to understand how transient HBV infections are resolved. In particular, to determine if infected hepatocytes containing covalently closed circular viral DNA (cccDNA) (Figure 2), are cleared from the liver by cell death or if they can be non-cytolytically “cured” by cytokines without cell death. Based on our previous work we believe that cell death plays a major role in recovery by promoting regeneration of liver cells leading to loss of cccDNA. Antibodies are also critical for recovery as they inactivate the virus and protect cells from re-infection. We propose to determine the relative contributions of hepatocyte death vs. cytokine mediated curing of hepatocytes in DHBV-infected ducks complementing our collaborative studies in woodchuck hepatitis virus (WHV) infected woodchucks and HBV-infected chimpanzees. The woodchuck and chimpanzee experiments are being performed in collaboration with Dr William Mason and Dr Robert Lanford.
Current work performed by Georget Reaiche is defining the timing of transient DHBV infection, the extent of cell-to-cell spread, and the variability between infected animals, particularly because the ducks we use are not inbred. We will then proceed to a detailed determination of the amount of hepatocyte death and regeneration that accompanies resolution of transient DHBV infection and we will look for histological evidence of cell death including inflammation, apoptosis and Kupffer cell activation. Analysis of liver tissue sections will determine whether the pattern of virus clearance is consistent with cell death or non-cytolytic curing of hepatocytes. We will also use primary duck embryonic hepatocytes to determine if cccDNA can survive cell division and if treatment with duck interferon-alpha and interferon-gamma can cure DHBV-infected hepatocytes that are passing through mitosis.
National Institutes of Health (NIH)
Royal Adelaide Hospital Research Committee
Faculty of Sciences, University of Adelaide