(182ak) Predicting the Effects of Mutations on Helper T Cell Immune Recognition of H1N1 Influenza Virus

In 2009, the H1N1 Influenza virus underwent antigenic shift, causing a pandemic. Since then, point mutations caused by antigen drift have continued to cause evolutionary changes in Influenza. Mutations in the viral proteins can affect protein stability, transmissibility, and immune evasion capabilities. There has been significant interest in understanding immune evasion caused by mutations to design better therapeutics. Although studies have been conducted on the effects of mutations on antibody binding, limited studies on how immune recognition of T cells have been done. In this study, we sought to predict the change in immune recognition of helper T cells for the H1N1 Influenza Virus between 2009 and 2017. Our results indicated there seems to be a trend for mutations to cause a decrease in immune recognition during the Northern Hemisphere’s Winter months.

This analysis was performed by determining consensus sequences, calculating binding scores for MHC alleles using ProPred, and then calculating a change in binding score. NCBI Influenza Database was first used to extract H1N1 Influenza protein sequences. These sequences were then grouped into subsets based on various levels of completeness and geographical location. Once complete, the sequences for each month and protein were submitted to ClustalOmega to align the sequences to determine the consensus sequence. The binding scores of the MHC were predicted using ProPred, an MHC Class II prediction algorithm. Finally, the change in binding is calculated using the difference between the wildtype month and a mutated month over the highest possible score for each allele. Different scores were created using allele frequency, ethnicity frequency, and relative protein abundance to look at various trends in the data. The allele frequency and ethnicity frequency were determined using allele data from the Allele Frequency Net Database, while the relative protein abundance was provided by literature.

At this point, the data shows that immune recognition typically decreases during the Northern Hemisphere's winter months. However, there appeared to be no trends in immune recognition changes during the other months. On average, 94% of the sequences presented each month were from the Northern Hemisphere, and 51% of the Northern Hemisphere came from the United States. Continued work to investigate the mutations that cause changes in immune recognition, specifically in months with significant modifications compared to other months, is being performed.