Poster Presentation Lorne Infection and Immunity 2014

Down-regulation of IFN-γ expression and IL-18 mediated cell signalling by hepatitis B virus. (#164)

Sinthujan Jegaskanda 1 , Sang H Ahn 2 3 , Narelle Skinner 1 , Alex Thompson 1 3 4 , Tin Ngyuen 3 4 , Jacinta Holmes 4 5 , Robert De Rose 1 , Marjon Navis 1 , Wendy R Winnall 1 , Marit Kramski 1 , Giovanna Bernardi 1 , Julianne Bayliss 3 , Danni Colledge 3 , Kumar Visvanathan 1 , Stephen Locarnini 3 , Stephen J. Kent 1 , Peter A Revill 1 3
  1. University of Melbourne, Parkville, VIC, Australia
  2. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
  3. Division of Research and Molecular Development, , Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia
  4. Department of Gastroenterology, St. Vincents Hospital, Fitzroy, Victoria, Australia
  5. WHO Collaborating Centre for Reference and Research on Influenza, Parkville, Victoria, Australia

The mechanisms by which hepatitis B virus (HBV) establishes and maintains chronic hepatitis B infection (CHB) are poorly defined.  Innate immune responses play a critical role in reducing HBV replication and pathogenesis. HBV has developed numerous mechanisms to escape these responses including the production of the secreted hepatitis B e antigen (HBeAg), which has been shown to regulate the antiviral toll like receptor (TLR) and interleukin 1 (IL-1) signalling. IL-18 is a related cytokine that inhibits HBV replication in hepatoma cell lines and the liver via induction of interferon gamma (IFN-γ) in NK cells and T cells.   We hypothesized that HBV, or HBV proteins modulate NK cell IFN-γ expression as an accessory immunomodulatory function.  We show that HBeAg protein, down-regulates NK cell IFN-γ expression. Additionally IFN-γ expression was significantly inhibited by exposure to serum from individuals with HBeAg-positive, but not HBeAg-negative chronic HBV infection.  We also show that the HBeAg protein suppresses IL-18 mediated NF- kB signalling in hepatoma cells whereas the related HBV core protein did not. Together these findings show that the HBeAg is an important regulator of IL-18 signalling and IFN-γ expression, which may be important in establishment and/or maintenance of persistent HBV infection.