There is currently no vaccine for Hepatitis C virus (HCV). The envelope glycoprotein complex, E1E2, is the sole target of neutralizing antibodies which makes it the critical component for a vaccine candidate. Like many viral glycoproteins, the E1E2 complex is coated in host-derived N-linked glycans which act to efficiently ‘shield’ the underlying protein surface and hinder antibody recognition, as well as supporting native protein folding. Interrogating the glycosylation of HCV E1E2 using LC-MS in combination with cryoEM has revealed two glycans that are required for correct E1E2 association, as well as highlighting a novel glycan site within a non-canonical N-linked glycan site. Using Byos, we have been able to decipher the glycan compositions and site occupancy that have contributed to an understanding of what native-like E1E2 looks like and will support the design of HCV vaccines.
This session was recorded in Jan 2023.