Researchers will investigate why immune system fails to control hepatitis C

A research consortium based at Massachusetts General Hospital (MGH) has been awarded $15 million from the National Institute of Allergy and Infectious Diseases to investigate how the hepatitis C virus (HCV) resists suppression and clearance by the immune system. The five-year grant will support a Cooperative Center for Translational Research in Human Immunology, which also will focus on how some individuals successfully recover from HCV while the infection becomes chronic in most of those infected, with a special emphasis on immunological events in the liver as the site of HCV replication.

"Hepatitis C is a major global health problem for which existing therapies are inadequate," says Raymond Chung, MD, director of Hepatology in the MGH Gastrointestinal Unit and co-director of the research center. "Improving our understanding of how and why the virus consistently evades immune system control should lead us to better ways of treating hepatitis C and possibly other chronic viral infections." Chung will lead a project to better define the role of the liver cells called hepatocytes in the innate and adaptive immune response to HCV infection.

Center co-director Paul Klenerman, PhD, of Oxford University will examine properties of the T cells that migrate to the liver in response to HCV infection. Additional principal investigators and project goals are:

• Georg Lauer, MD, PhD, MGH Gastrointestinal Unit, and John Wherry, PhD, Wistar Institute - investigate the functional capacity of CD4 and CD8 T cells within the liver in chronic HCV infection;
  
• Todd Allen, PhD, Ragon Institute of MGH, MIT and Harvard, and Matthew Henn, PhD, Broad Institute of MIT and Harvard - examine how selection pressure applied by T cells affects HCV evolution;
  
• Gordon Freeman, PhD, Dana-Farber Cancer Institute - develop a panel of reagents designed to modulate signaling in key immune cells;
  
• Joseph Misdraji, MD, MGH Pathology - create a library of liver cells and tissue from HCV-infected and uninfected patients to use in study experiments;
  
• Nicholas Haining, MB, ChB, Dana-Farber - develop high-throughput technology platforms to examine and modulate signals inhibiting the immune response.

Almost 170 million people worldwide are infected with HCV, 50 to 80 percent of whom will develop chronic hepatitis, which can lead to cirrhosis, liver cancer or liver failure. Identifying the factors that allow HCV to survive in spite of the immune response against the virus may also improve understanding of immune system failure in other chronic infections, including HIV, Epstein-Barr virus, and tuberculosis.

Source: Massachusetts General Hospital