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To spread, nervous system viruses sabotage cell, hijack transportation
Date:5/30/2012

s that occur throughout the cell. For the strenuous task of long distance intercellular communication, mitochondria move along the axon and synapses, sites of cell-to-cell contact where signaling occurs.

Calcium plays a key role in this cell communication, Kramer explained. A neuron experiences a spike in calcium levels in the axon and synapses when it receives a signal from another neuron. Though a natural rover, mitochondria contain a protein called Miro that detects this rush of calcium and stops the organelles in the synapse. The mitochondria then provide energy as the cell passes a signal along to the next neuron.

Through live-cell imaging of neurons grown in the Enquist lab, Kramer and Enquist observed how this process becomes corrupted by HSV-1 and PRV and how the viruses need the process to spread.

The chaos begins when the virus ramps up the neuron's firing of electrical signals, as was first reported in a 2009 paper published in the journal PLoS Pathogens by Enquist; first author Kelly McCarthy, a past member of Enquist's lab who received her doctoral degree from Princeton in 2011; and David Tank, the Henry L. Hillman Professor of Molecular Biology and co-director of the Princeton Neuroscience Institute.

In the latest research, Kramer and Enquist found that this spike in electrical activity floods the axon and synapses with calcium. As a consequence, the Miro proteins detect the increase in calcium and stop mitochondrial motion. The virus' control over the cell immediately dropped off, however, when Kramer and Enquist interfered with Miro's ability to respond to the uptick in calcium levels. Though the viral infection was not completely disrupted, it could not spread within or to other cells with the same efficiency.

Based on these observations, Kramer and Enquist suggest that viruses such as HSV-1 and PRV may bring mitochondria to a standstill in order to hijack their transportation. Mitochondria move about t
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Contact: Morgan Kelly
mgnkelly@princeton.edu
609-258-5729
Princeton University
Source:Eurekalert  

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