Authors:

Nicole Martinez

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About Paper:

Affecting over 50 million people and causing 250,000 deaths annually, Hepatitis C virus (HCV) remains a major global health challenge with no approved vaccine. HCV is an RNA virus whose envelope glycoproteins, E1 and E2, form a heterodimer critical for host cell entry. The virus's high genetic variability and lack of a definitive structural model have long hindered efforts to design highly effective vaccines and identify conserved regions targeted by broadly neutralizing antibodies (bNAbs). Recent studies have made substantial progress by resolving more comprehensive structures of the E1E2 heterodimer in complex with human bNAbs, offering new insights into conformational dynamics, epitope accessibility, and potential immune vulnerabilities. This research evaluates recent structural models of the E1E2 complex, focusing on differences between Protein Data Bank (PDB) entries 8RJJ and 7T6X and their interactions with bNAbs. Using PyMOL and structural analysis, five bNAbs and their corresponding E2 sequence residues were examined to assess how each epitope region aligns with the active binding surface of the antibody and the referenced complexes. This approach allowed for precise mapping of epitope positions relative to structural variations, showing that antibodies can bind similar epitope sequences even when the epitopes are in different conformations. Crucially, the antibody-binding landscapes of 8RJJ and 7T6X exhibited important conformational differences regarding the flexible E2 front layer, altering bNAb engagement and epitope accessibility. These findings reveal that epitope presentation depends on structural context. HC11 and AR4A, a non-competing antibody pair, bind E1E2 across conformations, aiding conserved epitope mapping and informing vaccine and immunology research. Keywords: Hepatitis C Virus (HCV); E1E2 Glycoprotein Heterodimer; Structural Virology; Epitope Mapping; Conformational Dynamics

Source:

Purdue University / 2025

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Co-authors:

Nicole Martinez