Immunology of Viral Hepatitis

The Immunology of Viral Hepatitis at UCL brings together basic and translational immunology with virology and with clinical investigators at UCL and the North Central London Viral Hepatitis Network to study hepatitis B and Hepatitis C. Research is focused on investigating the basis of chronicity of infection with HBV and HCV with the specific goal of identifying and developing interventions to limit damage in chronic infection and promote viral clearance by host immune mechanisms. Ongoing studies encompass investigation of the role of T cells, natural killer cells, dendritic cell biology and the development of immunomodulatory therapies, T cell re-programming and therapeutic vaccines for viral hepatitis.

William Rosenberg, based at the Institute of Hepatology, recently joined UCL with over a decade of experience directing the Wellcome Trust Clinical Research Facility in his previous post at Southampton University. He has made a major contribution to the discovery, validation and clinical application of biomarkers to monitor liver fibrosis in chronic liver disease. He is also working on dendritic cell biology and TLR agonists in the context of viral hepatitis.

Mala K Maini, based in the Division of Infection and Immunity in the Windeyer Building is a clinician scientist who has worked for many years on T cell responses in chronic viral infections (EBV, HIV-1 and 2, HCV, HBV). She now heads a group of basic and clinical scientists all working on intergrating aspects of the immunopathogenesis of chronic HBV infection. Their work uses samples from the viral hepatitis clinics she does with Richard Gilson (UCL) and Geoffrey Dusheiko (Royal Free Hospital) to dissect out components of the immune response contributing to viral control versus liver damage.

[Note: links are provided to the People pages on the School of Life and Medical Sciences website.  You can find out further information about research publications on the UCL Publications Database.]

Key Scientific Contributions

-  Differences in clonality of CD4 and CD8 pools in healthy and EBV-infected humans;

- Capacity of T cells to escape immune senescence by telomerase induction in viral infection;

- Enhanced functional flexibility of CD8 responses in HIV-2 infection

- HLA-peptide tetramers for the study of HBV-specific CD8 responses

- HBV-specific CD8 in patients controlling HBV; non-specific lymphocytic influx correlates with liver damage;

- NK cells contribute to HBV-related liver damage through TRAIL pathway;

- HBV-specific CD8 T cell attrition through Bim-mediated apoptosis;

- Reconstitution of HBV-specific T cells on treatment of HBV/HIV co-infected patients

- Influence of liver microenvironment on T cell signaling and antiviral function in HBV

- Early immune events in acute HBV infection

Key Collaborators

within UCL: Arne Akbar, Claudia Mauri, Paul Kellam, Geoffrey Dusheiko, Michael Jacobs, Richard Gilson, Nathan Richardson, William Rosenberg, Mary Collins

within UK: Paul Klenerman (Oxford), David Adams (Birmingham), Graeme Alexander (Cambridge), John Trowsdale (Cambridge)

Internationally: Antonio Bertoletti (Singapore), Maurizia Brunetta (Pisa), Pietro Lampertico (Milan), Maimuna Mendy (The Gambia), Luca Guidotti (Scripps and Milan), Pietro Andreone and Florian Bihl (Bologna)

Key publications

Guha IN, Parkes J, Roderick P, Chattopadhyay D, Cross R, Harris S, Kaye P, Burt AD, Ryder SD, Aithal GP, Day CP, Rosenberg WM. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology. 2008 Feb;47(2):455-60

Rosenberg WM, Voelker M, Thiel R, Becka M, Burt A, Schuppan D, Hubscher S, Roskams T, Pinzani M, Arthur MJ; European Liver Fibrosis Group. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004 Dec;127(6):1704-13

Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, Cheng J, Goedert JJ, Vlahov D, Hilgartner M, Cox S, Little AM, Alexander GJ, Cramp ME, O'Brien SJ, Rosenberg WM, Thomas DL, Carrington M. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science. 2004 Aug 6;305(5685):872-4.

Maini MK, Boni C, Lee CK, Larrubia JR, Reignat S, Ogg GS, King AS, Herberg J, Gilson R, Alisa A, Williams R, Vergani D, Naoumov NV, Ferrari C, Bertoletti A. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. Journal of Experimental Medicine. 2000 Apr 17;191(8):1269-80

Lascar RM, Gilson RJC, Lopes AR, Bertoletti A, Maini MK. Reconstitution of hepatitis B virus (HBV)-specific T cell responses on treatment of HIV/HBV co-infection. Journal of Infectious Diseases 2003 Dec 15; 188: 1815-19

Dunn C, Brunetto M, Reynolds G, Christophides T, Kennedy PT, Lampertico P, Das A, Lopes AR, Borrow P, Williams K, Humphreys E, Afford S, Adams DH, Bertoletti A, Maini MK. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. Journal of Experimental Medicine 2007;204:667-80 Patent through UCL Business on ideas arising from this work; Listed in JEM Top Ten Downloaded Articles Jan 2008

Lopes AR, Kellam P, Das A, Dunn C, Kwan A, Turner J, Peppa D, Gilson RJ, Gehring A, Bertoletti A, Maini MK. Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control hepatitis B virus. Journal of Clinical Investigation, May 2008

Das A, Hoare M, Davies N, Lopes AR, Dunn C, Kennedy PT, Alexander G, Finney H, Lawson A, Plunkett F, Akbar AN, Bertoletti A, Maini MK. Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. Journal of Experimental Medicine 2008, 205:2111-24

"Research Highlight" in JEM, Nature Medicine and Nature Reviews Immunology

Dunn C, Peppa D, Khanna P, Nebbia G, Jones M, Brendish N, Lascar RM, Brown D, Gilson RJ, Tedder RJ, Dusheiko G, Jacobs M, Klenerman P, Maini MK. Temporal analysis of early immune responses in patients with acute Hepatitis B virus infection. Gastroenterology 2009 in press

Page last modified on 07 oct 09 15:58 by Karen Rumsey