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Journal of Virology, September 2009, p. 8315-8326, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00633-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Anterograde Spread of Herpes Simplex Virus Type 1 Requires Glycoprotein E and Glycoprotein I but Not Us9{triangledown}

Helen M. McGraw,{dagger} Sita Awasthi,{dagger} Jason A. Wojcechowskyj, and Harvey M. Friedman*

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6073

Received 26 March 2009/ Accepted 9 June 2009

Anterograde neuronal spread (i.e., spread from the neuron cell body toward the axon terminus) is a critical component of the alphaherpesvirus life cycle. Three viral proteins, gE, gI, and Us9, have been implicated in alphaherpesvirus anterograde spread in several animal models and neuron culture systems. We sought to better define the roles of gE, gI, and Us9 in herpes simplex virus type 1 (HSV-1) anterograde spread using a compartmentalized primary neuron culture system. We found that no anterograde spread occurred in the absence of gE or gI, indicating that these proteins are essential for HSV-1 anterograde spread. However, we did detect anterograde spread in the absence of Us9 using two independent Us9-deleted viruses. We confirmed the Us9 finding in different murine models of neuronal spread. We examined viral transport into the optic nerve and spread to the brain after retinal infection; the production of zosteriform disease after flank inoculation; and viral spread to the spinal cord after flank inoculation. In all models, anterograde spread occurred in the absence of Us9, although in some cases at reduced levels. This finding contrasts with gE- and gI-deleted viruses, which displayed no anterograde spread in any animal model. Thus, gE and gI are essential for HSV-1 anterograde spread, while Us9 is dispensable.


* Corresponding author. Mailing address: 502 Johnson Pavilion, University of Pennsylvania, Philadelphia, PA 19104-6073. Phone: (215) 662-3557. Fax: (215) 349-5111. E-mail: hfriedma{at}mail.med.upenn.edu

{triangledown} Published ahead of print on 1 July 2009.

{dagger} H.M.M. and S.A. contributed equally to this work.


Journal of Virology, September 2009, p. 8315-8326, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00633-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.