An estimated 180 million people are infected with hepatitis C virus (HCV) worldwide and ~350.000 HCV-associated deaths per year indicate that HCV is one of the most important viral pathogens in humans. The HCV infection proceeds in about 70-80% of the cases to the chronic phase, mostly because the human organism does not find suitable defense mechanisms to clear the virus during the acute phase. One of the most important defense mechanism of the immune system to counteract viral infections are neutralizing antibodies, which bind to specific surface features of the virus and thereby block the infection of the host cell. HCV has developed numerous strategies to undermine the production and/or neutralizing activity of these antibodies.
Thomas Krey and his group investigate the interactions of neutralizing antibodies with HCV surface features located in the viral glycoproteins – also termed neutralization epitopes – by X-ray crystallography. They determine the 3D structure of these epitopes in complex with specific antibodies. Combined with a functional analysis of the neutralization activity of these antibodies these structures enable the researchers to draw conclusions on the efficiency of these epitopes to elicit particularly potent neutralizing antibodies and therefore on the suitability of these epitopes for informed vaccine design.
To date, our understanding of the three-dimensional arrangement of the viral glycoproteins E1 and E2 present at the virus surface is limited, but such structural knowledge has paved the way for more efficient vaccine candidates in other viral infections like Influenza virus or HIV. Therefore, Thomas Krey and his group concentrate on the structural analysis of an HCV glycoprotein in its native conformation that is assembled in the same way as the one in infectious viral particles.