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

Abstract

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 TCRβ repertoires were explored. Here, we reported that mEV71 infection impacted host brainstem TCRβ repertoire, where mEV71 infection skewed TCRβ diversity, changed VJ combination usages, and further expanded specific TCRβ CDR3 clones. Using bioinformatics analysis and ligand-binding prediction, we speculated the expanded TCRβ 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 TCRβ repertoire and presumably expanded VP1-specific TCRβ CDR3 in mEV71-infected mouse brainstem that integrated EV71 pathogenesis in central nervous system.

Activation of Host Cellular Signaling and Mechanism of Enterovirus 71 Viral Proteins Associated with Hand, Foot and Mouth Disease

“…The immune response of the host can be determined through the evaluation of the replication. In the process ofviral protein development, the host translation system translates the viral genome inside the host cytoplasm by the action of FUBP1 followed by an internal ribosome entry-transacting factor [ 19 ]. The internal changes that occur due to the outbreak of the viral protein lead to the suppression of antiviral and cap-dependent transcription by the presence of different signaling components such as PI4KB and immune responses, retinoic acid induced gene-I (RIG-I) as well as mitochondrial antiviral signaling protein (MAVS).…”

Activation of Host Cellular Signaling and Mechanism of EV71 Viral Proteins Associated with Hand, Foot and Mouth Disease

“…The immune response of the host can be determined through the evaluation of the replication. According to the development of the scope for viral protein development, the host translation system translates the viral genome inside the host cytoplasm by the action of FUBP1 followed by an internal ribosome entry-transacting factor [14]. The internal changes that occurred due to the outbreak of the viral protein have provided the condition for suppressing antiviral and cap-dependent transcription by the presence of different signalling components such as PI4KB and immune responses, RIG-I as well as MAVS.…”

The effects of SCARB2 and SELPLG gene polymorphisms on EV71 infection in hand, foot and mouth disease

“…HFMD is mainly caused by enterovirus A71 (EV71) [ 3 , 4 ], and EV71 infection might cause neurological, psychiatric complications, and even death [ 5 ]. In clinical practice, the symptoms of HFMD patients are usually mild and self-limiting, but a severe EV71 infection can lead to a diverse array of neurological diseases.…”