EEEV interferes with synaptic guidance and transmission via the SRCR/Ephrin RBD/Granulins/Sema and potassium channel-like systems

Researching the EEEV virus is challenging due to the virus's high lethality and significant risk. This study employed bioinformatics methods for domain search to investigate the pathogenesis and infection process of the EEEV virus P protein. The results demonstrated that the EEEV virus P protein contains domains that bind cholesterol/very low density lipoprotein, such as SRCR and lipid-binding serum glycoprotein. It also contains domains that interfere with synaptic guidance and transmission, such as ARF7 effector protein C-terminal, BAR, Ephrin RBD, Granulins, MHD1, Sema, TLC, transient receptor ion channel, ionotropic glutamate receptor, and voltage-dependent calcium channel alpha-2. Lastly, it contains domains that bind potassium ions, such as neurotransmitter-gated ion channel ligand-binding and neurotransmitter-gated ion channel transmembrane. This study reveals that the P protein of the EEEV virus binds to the synaptic membrane through the cholesterol/very low density lipoprotein domain. Then, it controls the activity of Ca2+ channels to make synaptic depolarization potentials or hyperpolarization potentials. These change how easily postsynaptic nerves can fire and mess up synaptic guidance. Then, similar to a potassium-ion transmembrane nerve channel, it inserts into the synaptic membrane. Its potassium ion channel function activates when bound to neurotransmitter ligands, directing the synaptic membrane to produce vesicles that encapsulate the EEEV virus and internalize it into the synapse.