Adaptation of Hepatitis C to Host HLA-Restricted Immune Responses in Australian Populations [ 2005 - 2007 ]

Research Grant

Researchers: Prof Simon Mallal (Principal investigator) ,  Dr Silvana Gaudieri ,  Prof Gary Jeffrey ,  Prof Gregory Dore

Brief description Over 200,000 Australians are infected with the Hepatitis C Virus (HCV) and about 11,000 new infections are diagnosed each year. Around 25% of people infected with HCV will clear the virus while for individuals with chronic infection 10 to 20% will develop cirrhosis of the liver within the next 20-40 years. Differences in host genetic factors and viral variants will, in large part, explain the observed heterogeneity in the clinical outcome and course of HCV infection. The basic theory underpinning this research is that the evolution of viruses such as HCV and HIV are influenced by the HLA type of the individual (hots), in combination with the ability of the virus to mutate (rid itself of deleterious mutations) to avoid the host's immune challenge (analogous to drug resistance) even at the lesser cost of impairing viral fitness or replication. We have shown that this is dependent on the immune environment that the virus encounters in relation to which HLA alleles are present in the host, therefore the escape is context specific. After transmission to a new host who lacks the same HLA type, the virus eliminates the previously advantageous mutations which could potentially impair viral fitness. The current study will carry out HCV sequencing and HLA typing on approximately 500 people with HCV from multiple Centres in Australia in order to characterise the interaction between the viral and host genetic factors. A customised software programme, Epipop, has been designed to perform sophisticated statistical analyses on the generated data, and has been successfully applied to HIV vaccine design. The results of this study could help explain why some infected individuals can spontaneously clear their infection while others go on to severe liver disease and allow clinicians to anticipate the course of infection in individuals and plan their management accordingly. Furthermore, the results may facilitate the search for optimal therapeutic and vaccination strategies.

Funding Amount $AUD 480,750.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant