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Journal of Virology, July 2007, p. 7286-7292, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02501-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Bystander Attenuation of Neuronal and Astrocyte Intercellular Communication by Murine Cytomegalovirus Infection of Glia{triangledown}

Winson S. C. Ho and Anthony N. van den Pol*

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520

Received 13 November 2006/ Accepted 18 April 2007

Astrocytes are the first cells infected by murine cytomegalovirus (MCMV) in primary cultures of brain. These cells play key roles in intercellular signaling and neuronal development, and they modulate synaptic activity within the nervous system. Using ratiometric fura-2 digital calcium imaging of >8,000 neurons and glia, we found that MCMV-infected astrocytes showed an increase in intracellular basal calcium levels and an enhanced response to neuroactive substances, including glutamate and ATP, and to high potassium levels. Cultured neurons with no sign of MCMV infection showed attenuated synaptic signaling after infection of the underlying astrocyte substrate, and intercellular communication between astrocytes with no sign of infection was reduced by the presence of infected glia. These bystander effects would tend to cause further deterioration of cellular communication in the brain in addition to the problems caused by the loss of directly infected cells.


* Corresponding author. Mailing address: Department of Neurosurgery-Room LSOG 212, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520. Phone: (203) 785-5823. Fax: (203) 737-2159. E-mail: anthony.vandenpol{at}yale.edu

{triangledown} Published ahead of print on 25 April 2007.


Journal of Virology, July 2007, p. 7286-7292, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02501-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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