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Journal of Virology, October 2007, p. 10742-10757, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00981-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Glycoprotein D-Independent Spread of Pseudorabies Virus Infection in Cultured Peripheral Nervous System Neurons in a Compartmented System{triangledown}

T. H. Ch'ng,1,{dagger} P. G. Spear,2 F. Struyf,2,{ddagger} and L. W. Enquist1*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544,1 Department of Microbiology and Immunology, Northwestern University, Evanston, Illinois 602082

Received 7 May 2007/ Accepted 18 July 2007

The molecular mechanisms underlying the directional neuron-to-epithelial cell transport of herpesvirus particles during infection are poorly understood. To study the role of the viral glycoprotein D (gD) in the directional spread of herpes simplex virus (HSV) and pseudorabies virus (PRV) infection, a culture system consisting of sympathetic neurons or epithelial cells in different compartments was employed. We discovered that PRV infection could spread efficiently from neurons to cells and back to neurons in the absence of gD, the viral ligand required for entry of extracellular particles. Unexpectedly, PRV infection can also spread transneuronally via axo-axonal contacts. We show that this form of interaxonal spread between neurons is gD independent and is not mediated by extracellular virions. We also found that unlike PRV gD, HSV-1 gD is required for neuron-to-cell spread of infection. Neither of the host cell gD receptors (HVEM and nectin-1) is required in target primary fibroblasts for neuron-to-cell spread of HSV-1 or PRV infection.


* Corresponding author. Mailing address: Schultz Laboratory, Department of Molecular Biology, Princeton University, Princeton, NJ 08544. Phone: (609) 258-2415. Fax: (609) 258-1035. E-mail: lenquist{at}princeton.edu

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

{dagger} Present address: University of California at Los Angeles, 695 Charles E. Young Dr. S., 3524 Gonda Research Building, Los Angeles, CA 90055.

{ddagger} Present address: GlaxoSmithKline, 1330 Rixensart, Belgium.


Journal of Virology, October 2007, p. 10742-10757, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00981-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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