Pathogenic rabies virus alters host protein expression in the central nervous system: implications for neuronal...

Area of Science:

• Neurovirology
• Proteomics
• Molecular Biology

Background:

• Rabies virus (RABV) poses a significant threat, causing fatal neurological disease.
• Understanding RABV's impact on host cells, particularly neurons, is crucial for developing effective treatments.

Purpose of the Study:

• To investigate host protein expression changes in response to RABV infection using proteomics.
• To elucidate the molecular mechanisms underlying RABV-induced neuronal dysfunction.

Main Methods:

• Proteomic analysis of host responses in mice infected with wild-type RABV.
• Quantification of protein expression levels related to ion homeostasis and synaptic vesicle function.

Main Results:

• RABV infection altered proteins involved in ion homeostasis: H+ ATPase and Na+/K+ ATPase were upregulated, while Ca2+ ATPase was downregulated, reducing intracellular Na+ and Ca2+.
• Downregulation of SNARE proteins (e.g., alpha-SNAP, TRIM9, syntaxin, pallidin) essential for synaptic vesicle docking and fusion was observed.
• Accumulation of synaptic vesicles in presynapses of RABV-infected mice.

Conclusions:

• RABV infection significantly alters host protein expression, impacting ion homeostasis and synaptic vesicle trafficking.
• These proteomic alterations provide insights into the mechanisms of RABV-induced neuronal dysfunction.
• The findings highlight potential therapeutic targets for mitigating rabies virus's neurological effects.