LAUSR

Mutations arise in the genomes of progeny viruses during infection. Mutations that occur in epitopes targeted by host antibodies allow the progeny virus to escape the host adaptive, B-cell mediated antibody immune response. Major epitopes have been identified in influenza B virus (IBV) hemagglutinin (HA) protein. However, IBV strains maintain a seasonal presence in the human population and changes in IBV genomes in response to immune pressure are not well characterized. There are two lineages of IBV that have circulated in the human population since the 1980s, B-Victoria and B-Yamagata. It is hypothesized that early exposure to one influenza subtype leads to immunodominance. Subsequent seasonal vaccination or exposure to new subtypes may modify subsequent immune responses, which, in turn, results in selection of escape mutations in the viral genome. Here we show that while some mutations do occur in known epitopes suggesting antibody escape, many mutations occur in other parts of the HA protein. Analysis of mutations outside of the known epitopes revealed that these mutations occurred at the same amino acid position in viruses from each of the two IBV lineages. Interestingly, where the amino acid sequence differed between viruses from each lineage, reciprocal amino acid changes were observed. That is, the virus from the Yamagata lineage become more like the Victoria lineage virus and vice versa. Our results suggest that some IBV HA sequences are constrained to specific amino acid codons when viruses are cultured in the presence of antibodies. Some changes to the known antigenic regions may also be restricted in a lineage-dependent manner. Questions remain regarding the mechanisms underlying these results. The presence of amino acid residues that are constrained within the HA may provide a new target for universal vaccines for IBV.