The role of ion channels during rabies virus infection

Rabies virus (RABV) is a single-stranded negative sense RNA virus of the genus Lyssavirus that causes 40,000-70,000 reported deaths annually. The number of actual deaths is estimated as up to 100 times higher since only 2-3% of human cases are thought to be reported. As 40% of RABV infected individuals are children, the years of life lost due to RABV makes it the seventh most important global infectious disease.

RABV transmission typically occurs from bites or scratches of infected animals. RABV targets neuronal cells and has been shown to modulate their ion channel function. A more detailed understanding of which host cell ion channels are involved (and in what manner) in RABV pathogenesis is required in order to develop new therapeutic approaches for the treatment of infection. Ion channels are attractive drug targets as their pharmacology is well established with activators and inhibitors being administered to patient’s everyday.

This proposal will identify the specific ion channels manipulated during a RABV infection of human neuronal tissue. The specific ion channels modulated by RABV will then be targeted with specific and existing ion channel drugs as alternative human and animal RABV therapies.

The key technique used will be patch clamp analysis to determine changes in ion channel currents between primary neuronal cell cultures expressing pathogenic or attenuated RABV proteins.