Proteomic profiling reveals that rabies virus infection results in differential expression of host proteins involved in ion homeostasis and synaptic physiology in the central nervous system.
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 Ca(2+) ATPase was down-regulated, which resulted in reduction of the intracellular Na(+) and Ca(2+) concentrations. Furthermore, infection with wt RV resulted in down-regulation of soluble NSF attachment receptor proteins (SNAREs) such as alpha-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.
Dhingra
Vikas
V
Department of Pathology, University of Georgia, Athens, Georgia 30602, USA.
Li
Xiaqing
X
Liu
Yuru
Y
Fu
Zhen F
ZF
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015180:Electrophoresis, Gel, Two-Dimensional; D006706:Homeostasis; D007150:Immunohistochemistry; D007477:Ions / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011188:Potassium / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics; D011818:Rabies / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D011820:Rabies virus / Q000472:pathogenicity / Q000502:physiology; D050600:SNARE Proteins / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D014774:Virulence
D007477:Ions; D011506:Proteins; D050600:SNARE Proteins; D012964:Sodium; D000251:Adenosine Triphosphatases; D011188:Potassium; D002118:Calcium