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J Virol, June 1998, p. 4580-4588, Vol. 72, No. 6
Department of Molecular Biology, Princeton
University, Princeton, New Jersey 08544
Received 5 December 1997/Accepted 24 February 1998
We describe use of developing chicken embryos as a model to study
neuronal spread and virulence of pseudorabies virus (PRV). At embryonic
day 12,
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
A Chicken Embryo Eye Model for the Analysis of
Alphaherpesvirus Neuronal Spread and Virulence
and
-galactosidase-expressing PRV strains were injected into the
vitreous humor of one eye, and virus replication and spread from the
eye to the brain were measured by
-galactosidase activity and the
recovery of infectious virus from tissues. The wild-type PRV strain,
Becker, replicated in the eye and then spread to the brain, causing
extensive pathology characterized by edema, hemorrhage, and necrosis
that localized to virally infected tissue. The attenuated vaccine
strain, Bartha, replicated in the eye and spread throughout specific
regions of the brain, producing little to no overt pathology. Becker
mutants lacking membrane proteins gE or gI replicated in the eye and
were able to spread to the brain efficiently. The pathology associated
with replication of these mutants in the brain was intermediate to that
induced by Becker or Bartha. Mixed infection of a gE deletion mutant
and a gI deletion mutant restored the pathogenic phenotype to wild-type levels. These data indicate that the replication of virus in embryonic brain tissue is not sufficient to induce the characteristic
pathological response and that the gE and gI gene products actively
affect pathological responses in the developing chicken brain.
*
Corresponding author. Mailing address: Department of
Molecular Biology, Princeton University, Princeton, NJ 08544. Phone: (609) 258-2415. Fax: (609) 258-1035. E-mail:
lenquist{at}molbiol.princeton.edu.
Present address: Department of Metabolic Disease, Bristol-Myers
Squibb, Princeton, NJ 08543.
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