Abstract
To understand how rabies virus (RV) infection results in neuronal dysfunction, the authors employed proteomics technology to profile host responses to RV infection. In mice infected with wild-type (wt) RV, the expression of proteins involved in ion homeostasis was altered. H+ ATPase and Na+/K+ ATPase were up-regulated whereas Ca2+ ATPase was down-regulated, which resulted in reduction of the intracellular Na+ and Ca2+ concentrations. Furthermore, infection with wt RV resulted in down-regulation of soluble NSF attachment receptor proteins (SNAREs) such as α-synaptosome-associated protein (SNAP), tripartite motif-containing 9 (TRIM9), syntaxin, and pallidin, all of which are involved in docking and fusion of synaptic vesicles to and with presynaptic membrane. As a consequence, accumulation of synaptic vesicles was observed in the presynapses of mice infected with wt RV. These data demonstrate that infection with wt RV results in alteration of host protein expression, particularly those involved in ion homeostasis and docking and fusion of synaptic vesicles to presynaptic membrane, which may lead to neuronal dysfunction. On the other hand, attenuated RV up-regulated the expression of proteins involved in the induction of apoptosis, explaining why apoptosis is observed only in cells or animals infected with attenuated RV in previous studies.
This work is supported partially by Public Health Service grant AI-051560 from the National Institute of Allergy and Infectious Diseases. The authors thank Luciana Sarmento for animal care and infection, Tesfai Tseggai for preparing BSR cells, and Mary Ard for help in electron microscopy. The authors express their gratitude to Dr. John Wagner, Department of Physiology and Toxicology, College of Veterinary Medicine, for critically reviewing this article.