Corticosteroids are unable to protect against pseudorabies virus-induced tissue damage in the developing brain.
After intraocular injection of the virulent pseudorabies virus (PRV) strain Becker into late-stage chicken embryos, the virus spreads and replicates in the brain, where severe edema and hemorrhaging follow. By contrast, the attenuated Bartha strain does not cause severe brain pathology despite viral replication and spread throughout the brain (B. W. Banfield, G. S. Yap, A. C. Knapp, and L. W. Enquist, J. Virol. 72:4580-4588, 1998). These observations prompted us to explore the mechanism by which the virulent Becker strain mediates pathology in the chicken embryo central nervous system (CNS). To test the hypothesis that Becker infection induced an inflammatory response in the developing CNS, we examined the ability of the anti-inflammatory corticosteroid dexamethasone (Dex) to protect chicken embryos from PRV-induced brain damage. We found that Dex is not sufficient to protect the chicken embryo CNS from damage due to Becker infection. Surprisingly, systemic Dex delivery appeared to potentiate CNS damage, which was preceded by petechial hemorrhaging in the optic lobes. Taken together, these data suggest that the severe pathology elicited during the Becker infection is due not to immunopathology but to damage by the virus itself, possibly through the damage to or destruction of endothelial cells.
Clase
Amanda C
AC
Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Banfield
Bruce W
BW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001921:Brain / Q000196:embryology* / Q000473:pathology / Q000821:virology*; D002642:Chick Embryo; D003907:Dexamethasone / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology / Q000821:virology; D005123:Eye / Q000821:virology; D011558:Herpesvirus 1, Suid / Q000472:pathogenicity*; D011557:Pseudorabies / Q000473:pathology / Q000517:prevention & control*; D014774:Virulence
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone