Dr Allison Jilbert

• Biography/ Background

  Allison was appointed as an academic staff member of the School of Molecular and Biomedical Science in September 2008. She is responsible for the design and co-ordination of the undergraduate and post-graduate Virology teaching programs and is head of the Hepatitis Virus Research Group. Allison was previously affiliated with the Infectious Diseases Laboratories, of the Institute of Medical and Veterinary Science. Allison has extensive experience in hepatitis B virus research using the duck (DHBV), chimpanzee and woodchuck models of HBV infection. She has current funding for her laboratory from the NHMRC and NIH.

• Qualifications

  B.Sc., University of Melbourne, 1979;

  B.Sc. (Hons), University of Melbourne, 1980; 

  Ph.D., University of Adelaide, 1989;

  Fellow Australian Society for Microbiology (F.A.S.M.) 2011.

• Research Interests

  Despite the availability of a protective hepatitis B virus (HBV) vaccine, the number of cases of HBV infection continues to increase with 350 million HBV carriers worldwide. Chronic HBV infection is linked to high rates of liver disease, cirrhosis and primary liver cancer.

  The reason why some HBV infections are successfully resolved while others remain chronic is not known. Whatever the answer, it is now becoming clear that successful control of a chronic HBV infection by antiviral drug therapy will significantly reduce the normally high risk of progression to cirrhosis and liver cancer. Unfortunately, the current generation of antiviral drugs has a very low success rate, leading to virus clearance in no more than 20% of HBV carriers.

  Therefore, the major goal of the HBV Research Laboratory is to design improved therapies for chronic HBV infections to prevent progression to cirrhosis and liver cancer. This goal is being pursued through 3 lines of research with international collaborators that are being performed in the woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV) models and using HBV infected human and chimpanzee liver.

  1. Resolution of acute HBV infections:

  We are determining how the immune system resolves acute HBV infections and eliminates the stable nuclear form of HBV DNA, covalently closed circular DNA (cccDNA). Our previous data has indicated that extensive hepatocyte death with activation of Kupffer cells (liver macrophages) occurs during the recovery phase of acute WHV infections. These findings imply that therapies for chronic HBV infection also require extensive hepatocyte turnover to help eliminate cccDNA. Recent studies from the laboratory have determined that cccDNA is able to survive cell division and is the major form of residual DHBV DNA present in the liver following the resolution of acute infection making this a key target during the resolution of acute infection.

  2. Development of vaccines for treatment of chronic infections:

  We are developing novel vaccines against HBV infection including naked DNA, whole-cell DNA, and recombinant fowlpoxvirus vaccines, and testing them for their ability to protect against and to provide therapy for chronic DHBV infections. Our ultimate goal is to define a protocol for combination antiviral and vaccination treatments that either eliminates chronic HBV infection, or achieves a level of control of infection that minimises ongoing disease. This might occur by antiviral targeting of infected hepatocytes that cccDNA to reduce virus loads to virtually undetectable levels.

  3. Pre-malignant changes in the chronically infected liver:

  Studies are also underway to understand how the infected hepatocyte population changes during chronic HBV infection, and how these changes lead to the development of liver cancer. We hypothesize that during chronic HBV infection the immune response kills infected hepatocytes and provides and growth advantage to hepatocytes that can no longer be infected with HBV. This leads to the clonal proliferation of HBV-negative hepatocytes that over time become the major cell population in the liver. We have evidence for extensive clonal proliferation of hepatocytes in woodchucks with chronic WHV infection and have recently found similar levels of proliferation in the liver of chimpanzees and humans with chronic HBV infection. Further studies are underway.

• Research Funding

  • NHMRC Project Grant 2011-2013; #1004847; CIA: A.R. Jilbert, CIB: W.S. Mason, CIC G.Y. Reaiche; "Hepatitis B virus covalently closed circular DNA"
  • NHMRC Project Grant 2007-2010; #453505; CIA: A.R. Jilbert, CIB: W.S. Mason; "Resolution of transient hepatitis B virus infections"
  • NHMRC Project Grant 2007-2010; #453506; CIA: A.R. Jilbert; "Immune therapies for chronic hepatitis B virus infection"
  • NHMRC Project Grant 2007-2010; #453507; CIA: A.R. Jilbert, CIB: W.S. Mason, CID: H.A.J. Harley; "Clonal proliferation of hepatocytes and progression of liver disease in chronic hepatitis B virus infection"
  • National Institutes of Health R21 Research and Development Grant; CIA: R Lanford, CIB: W.S. Mason, CIC: A.R. Jilbert; "Resolution of transient HBV infection in chimpanzees"
  • National Institutes of Health R01 Grant. CIA: F. Chisari, CIB: S. Wieland, CIC: R. Purcell CID: A.R. Jilbert. "Pathogenesis of Liver Disease in Hepatitis"
  • REPLICor Inc Research Collaboration. CIA: A.R. Jilbert, CIB: F. Noordeen. Testing the ability of Phosphorothioate Oligonucleotides (PS-ONs) to inhibit DHBV infection in vitro and in vivo.
  • Gilead Sciences Pty Ltd Research Collaboration. CIA: A.R. Jilbert. "Antiviral efficacy of tenofovir in combination with emtricitabine in the duck model of HBV infection"

• Publications

  Miller DS, Halpern M, Kotlarski I, Jilbert AR (2006a). Vaccination of ducks with a whole-cell vaccine expressing duck hepatitis B virus core antigen elicits antiviral immune responses that enable rapid resolution of de novo infection. Virology. 348(2):297-308.

  Miller DS, Kotlarski I, Jilbert AR (2006b). DNA vaccines expressing the duck hepatitis B virus surface proteins lead to reduced numbers of infected cells and protect ducks against the development of chronic infection in a virus dose dependent manner. Virology. 351 (1):159-69.

  Xu C, Yamamoto T, Zhou T, Aldrich, CE Frank K, Cullen J, Jilbert AR, Mason WS (2007). The liver of woodchucks chronically infected with the woodchuck hepatitis virus contains foci of virus core antigen negative hepatocytes with both altered and normal morphology. Virology. 359(2):283-94.

  Miller DS, Boyle D, Feng F, Reaiche GY, Kotlarski I, Colonno R, Jilbert AR (2008). Antiviral therapy with entecavir combined with post-exposure "prime-boost" vaccination eliminates duck hepatitis B virus infected hepatocytes and prevents the development of persistent infection. Virology 373:329-41.

  Jilbert AR, Mason WS (2008). Hepadnaviruses of birds. Encyclopedia of Virology, 3rd Edition. B.W.J. Mahy and M.H.V. Van Regenmortel Editors, Volume 2 pp. 327-335. Oxford: Elsevier.

  Jilbert AR, Mason WS, Kann M (2008). Hepatitis B virus replication. In: Hepatitis B virus Human Virus Guide, Chapter 4. 2nd Edition. Edited by Stephen Locarnini and CL Lai, International Medical Press. Pp 4.1 - 4.13.

  Jilbert AR, Litwin S, Mason WS (2008). Pathogenesis of Hepatitis B Virus Infections. In: Hepatitis B virus Human Virus Guide, Chapter 7. 2nd Edition. Edited by Stephen Locarnini and CL Lai, International Medical Press. Pp 7.1 - 7.17.

  Cao F, Scougall CA, Jilbert AR, Tavis JE (2009). Pre-P is a secreted glycoprotein encoded as an N-terminal extension of the duck hepatitis B virus polymerase gene. J. Virol. 2009 Feb; 83(3):1368-78.

  Mason WS, Xu C, Low HC, Saputelli J, Aldrich CE, Scougall C, Grosse A, Colonno R, Litwin S, Jilbert AR (2009). The amount of hepatocyte turnover that occurred during resolution of transient hepadnavirus infections was lower when virus replication was inhibited with entecavir. J. Virol. 2009 Feb 83(4):1778-89.

  Mason WS, Low HC, Xu C, Aldrich CE, Scougall CA, Grosse A, Clouston A, Chavez D, Litwin S, Peri S, Jilbert AR, Lanford RE. Detection of clonally expanded hepatocytes in chimpanzees with chronic hepatitis B virus infection. J Virol. 2009 Sep 83(17):8396-408.

• Professional Associations

  • Core Laboratory Leader, Australian Centre for Hepatitis Virology Inc (ACHV)
  • Group Leader, Australian Centre for HIV & Hepatitis Virology (ACH^2)
  • Member, Australian Society for Microbiology Inc (ASM)
  • Committee Member, Australian Virology Group (AVG5)
  • Co-convener, Adelaide Liver Research Group (ALRG)

• Professional Interests

  • Invited Speaker at National and International Research Meetings
  • Invited Organiser of National and International Research Conferences
  • NHMRC Grant Review Panel Member and ARC Oz Reader
  • Invited Research Grant Reviewer for National and International Research Councils
  • Reviewer for International Journals
  • Chair, International Committee on the Taxonomy of Viruses Study Group on Hepadnaviruses and Hepatitis Delta, 2005-2008

Entry last updated: Monday, 16 Apr 2012