Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin

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The influenza virus is one of the most rapidly evolving human viruses. Every year, it accumulates mutations that allow it to evade the host immune response of previously infected individuals. Which sites in the virus’ genome allow this immune escape and the manner of escape is not entirely understood, but conventional wisdom states that specific “immune epitope sites” in the protein hemagglutinin are preferentially attacked by host antibodies and that these sites mutate to directly avoid host recognition; as a result, these sites are commonly targeted by vaccine development efforts. Here, we combine influenza hemagglutinin sequence data, protein structural information, IEDB immune epitope data, and historical epitopes to demonstrate that neither the historical epitope groups nor epitopes based on IEDB data are crucial for predicting the rate of influenza evolution. Instead, we find that a simple geometrical model works best: sites that are closest to the location where the virus binds the human receptor and are exposed to solvent are the primary drivers of hemagglutinin evolution. There are two possible explanations for this result. First, the existing historical and IEDB epitope sites may not be the real antigenic sites in hemagglutinin. Second, alternatively, hemagglutinin antigenicity may not be the primary driver of influenza evolution.

Vyšlo v časopise: Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004940
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004940

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