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J Virol, May 1998, p. 4434-4441, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Different Patterns of Neuronal Infection after
Intracerebral Injection of Two Strains of Pseudorabies Virus
J. Patrick
Card,1,2,*
Pat
Levitt,3 and
Lynn W.
Enquist4
Departments of
Neuroscience,1
Neurobiology,3 and
Psychiatry,2 University of
Pittsburgh, Pittsburgh, Pennsylvania 15260, and
Department
of Molecular Biology, Princeton University, Princeton, New Jersey
085444
Received 6 October 1997/Accepted 5 February 1998
Pseudorabies virus (PRV), a swine neurotropic alphaherpesvirus, is
known to invade the central nervous system (CNS) of a variety of animal
species through peripherally projecting axons, replicate in the parent
neurons, and then pass transsynaptically to infect other neurons of a
circuit. Studies of the human pathogen herpes simplex virus type 1 have
reported differences in the direction of transport of two strains of
this virus after direct injection into the primate motor cortex. In the
present study we examined the direction of transport of virulent and
attenuated strains of PRV, utilizing injections into the rat prefrontal
cortex to evaluate specific movement of virus through CNS circuitry.
The data demonstrate strain-dependent patterns of infection consistent with bidirectional (anterograde and retrograde) transport of virulent virus and unidirectional (retrograde) transport of attenuated PRV from
the site of injection. The distribution of infected neurons and the
extent of transsynaptic passage also suggest that a release defect in
the attenuated strain reduces the apparent rate of viral transport
through neuronal circuitry. Finally, injection of different concentrations of virus influenced the onset of replication within a
neural circuit. Taken together, these data suggest that viral envelope
glycoproteins and virus concentration at the site of injection are
important determinants of the rate and direction of viral transport
through a multisynaptic circuit in the CNS.
*
Corresponding author. Mailing address: Department of
Neuroscience, 446 Crawford Hall, University of Pittsburgh, Pittsburgh, PA 15260. Phone: (412) 624-6995. Fax: (412) 624-9198. E-mail: Card{at}bns.pitt.edu.
J Virol, May 1998, p. 4434-4441, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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