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Journal of Virology, August 2002, p. 8310-8317, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8310-8317.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vivo Egress of an Alphaherpesvirus from Axons

Mark J. Tomishima,{dagger} and Lynn W. Enquist*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

Received 19 March 2002/ Accepted 6 May 2002

Many alphaherpesviruses establish a latent infection in the peripheral nervous systems of their hosts. This life cycle requires the virus to move long distances in axons toward the neuron's cell body during infection and away from the cell body during reactivation. While the events underlying entry of the virion into neurons during infection are understood in principle, no such consensus exists regarding viral egress from neurons after reactivation. In this study, we challenged two different models of viral egress from neurons by using pseudorabies virus (PRV) infection of the rat retina: does PRV egress solely from axon terminals, or can the virus egress from axon shafts as well as axon terminals? We took advantage of PRV gD mutants that are not infectious as extracellular particles but are capable of spreading by cell-cell contact. We observed that both wild-type virus and a PRV gD null mutant are capable of spreading from axons to closely apposed nonneuronal cells within the rat optic nerve after intravitreal infection. However, infection does not spread from these infected nonneuronal cells. We suggest that viral egress can occur sporadically along the length of infected axons and is not confined solely to axon terminals. Moreover, it is likely that extracellular particles are not involved in nonneuronal cell infections. Taking these together with previous data, we suggest a model of viral egress from neurons that unifies previous apparently contradictory data.

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

{dagger} Present address: Laboratory of Stem Cell and Tumor Biology, Neurosurgery and Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Journal of Virology, August 2002, p. 8310-8317, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8310-8317.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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