Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages.

摘要: ABSTRACT Numerous experimental studies have demonstrated that CD8 + T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising rigorous statistical tests failed find evidence of positive selection in the epitopes targeted cells. Here we use a novel computational approach test for T-cell epitopes. We define all nucleoprotein (NP) and matrix protein (M1) with experimentally identified human responses then compare evolution these parallel lineages swine viruses been diverging since roughly 1918. significant enrichment substitutions alter NP versus virus, consistent idea are under selection. Furthermore, show epitope-altering virus enriched on trunk branches phylogenetic tree, indicating acquire mutations selective advantage. However, even NP, sites evolve more slowly than do nonepitope sites, presumably because stronger inherent functional constraint. Overall, our work demonstrates there clear from illustrates how comparative analyses different hosts can identify otherwise obscured strong IMPORTANCE There interest correlates anti-influenza protective diverse strains. provide such broad immunity, they target conserved proteins. An important question whether sufficiently drive evolution. Although many shown limit replication animal models associated decreased symptoms humans, no proven significance evolves escape comparisons rigorously demonstrate pressure fix promote further advantage preferentially located “trunk” tree. results targeting play an role shaping