Molecular Immunovirology

DANIEL LAMARRE, Ph.D.

• Full Professor, Department of Medicine, Université de Montréal
• Université de Montréal Novartis/Canadian Liver Foundation Hepatology Research Chair
• Director, Hepatology/Gastro-enterology Research, Centre de recherche du Centre hospitalier de l’Université de Montréal (CHUM)

Hepatitis C virus (HCV) infection affects 3% of the population world wide and is a serious cause of liver disease with infected individuals at risk of developing significant morbidity and mortality. HCV has been remarkably adept at escaping the human immune system leading to a persistent infection in the majority of acute cases. Chronic infection is typical, and the disease course although unpredictable can lead to fibrosis, cirrhosis and liver cancer. The incidence of liver diseases, the fourth leading killer of Canadians by disease, kept increasing mainly due to chronic infection. Current therapies are sub-optimal, are poorly tolerated and often contraindications highlighting the unmet medical need for novel therapeutic approaches.

The study of HCV biology and the characterization of viral proteins essential for replication have recently led to the introduction of a novel class of viral enzyme target-based inhibitors (Lamarre et al., Nature 2003), which hold great promise to markedly improve treatments of Hepatitis C. Although HCV infection is one of the most widespread chronic infectious diseases, its natural pathogenesis and the mechanisms pertaining to viral persistence are rather still poorly understood. Both innate and adaptive immune responses play a key role in the control and resolution of acute infection. However, persistence may be explained by a decreasingly efficient immune response. The role of the immune responses and restoration of immune functions upon the interferon-based treatment of chronic hepatitis C are also not well understood. Recently, major advances in the characterisation of novel proteins of the Toll-Like Receptor TLR family and their downstream signalling pathways, have suggested a key role in recognition of specific components derived from pathogens including structures of viruses, which initiate the innate immune responses and lead to the adaptive immunity. The propensity of HCV to establish persistent infection indicates that the virus has evolved many strategies aimed at interfering with cellular antiviral pathways. The characterization of such viral evasion mechanisms represents an emerging field that may provide novel therapeutic based on restoration of the innate antiviral responses.

T + 514 343.7127
F + 514 343.7780
daniel.lamarre@umontreal.ca