Enterovirus 71 Infection Shapes Host T Cell Receptor Repertoire and Presumably Expands VP1-Specific TCRβ CDR3 Cluster

Enterovirus 71 (EV71) has become an important public health problem in the Asia-Pacific region in the past decades. EV71 infection might cause neurological and psychiatric complications and even death. Although an EV71 vaccine has been currently approved, there is no effective therapy for treating EV71-infected patients. Virus infections have been reported to shape host T cell receptor (TCR) repertoire. Therefore, understanding of host TCR repertoire in EV71 infection could better the knowledge in viral pathogenesis and further benefit the anti-viral therapy development. In this study, we used a mouse-adapted EV71 (mEV71) model to observe changes of host TCR repertoire in an EV71-infected central nervous system. Neonate mice were infected with mEV71 and mouse brainstem TCR beta repertoires were explored. Here, we reported that mEV71 infection impacted host brainstem TCR beta repertoire, where mEV71 infection skewed TCR beta diversity, changed VJ combination usages, and further expanded specific TCR beta CDR3 clones. Using bioinformatics analysis and ligand-binding prediction, we speculated the expanded TCR beta CDR3 clone harboring CASSLGANSDYTF sequence was capable of binding cleaved EV71 VP1 peptides in concert with major histocompatibility complex (MHC) molecules. We observed that mEV71 infection shaped host TCR beta repertoire and presumably expanded VP1-specific TCR beta CDR3 in mEV71-infected mouse brainstem that integrated EV71 pathogenesis in central nervous system.