Pathogenic Rabies Virus Alters Host Protein Expression in the Central Nervous System: Implications for Neuronal Dysfunction

摘要

Proteomics technology was employed to profile host responses to rabies virus (RABV) infection in order to understand how RABV infection results in neuronal dysfunction. In mice infected with wild-type (wt) RABV, the expression of proteins involved inion homeostasis was altered. H~+ ATPase and Na~+/K~+ ATPase were up-regulated while Ca~(2+) ATPase was down-regulated, which resulted in reduction of intracellular Na~+and Ca~(2+) concentrations. Furthermore, infection with wt RABV resulted in down-regulation of SNAREs such as alpha-SNAP, TRIM9, syntaxin, and pallidin, all of which are involved in docking and fusion of synaptic vesicles to and with the presynaptic membrane. As a consequence, the accumulation of synaptic vesicles was observed in the presynapses of mice infected with wt RABV. These data demonstrate that infection with wt RABV results in the alteration of host protein expression, particularly those involved in ion homeostasis and docking and the fusion of synaptic vesicles to the presynaptic membrane, which may lead to neuronal dysfunction.