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Journal of Virology, October 1999, p. 8781-8790, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Severity of Murray Valley Encephalitis in Mice Is Linked to Neutrophil Infiltration and Inducible Nitric Oxide Synthase Activity in the Central Nervous System

D. M. Andrews,1 V. B. Matthews,1 L. M. Sammels,1 A. C. Carrello,1 and P. C. McMinn1,2,*

Department of Microbiology, The University of Western Australia, Queen Elizabeth II Medical Center, Nedlands, WA 6009,1 and Department of Microbiology, Princess Margaret Hospital for Children, Subiaco, WA 6008,2 Australia

Received 19 April 1999/Accepted 15 July 1999

A study of immunopathology in the central nervous system (CNS) during infection with a virulent strain of Murray Valley encephalitis virus (MVE) in weanling Swiss mice following peripheral inoculation is presented. It has previously been shown that virus enters the murine CNS 4 days after peripheral inoculation, spreads to the anterior olfactory nucleus, the pyriform cortex, and the hippocampal formation at 5 days postinfection (p.i.), and then spreads throughout the cerebral cortex, caudate putamen, thalamus, and brain stem between 6 and 9 days p.i. (P. C. McMinn, L. Dalgarno, and R. C. Weir, Virology 220:414-423, 1996). Here we show that the encephalitis which develops in MVE-infected mice from 5 days p.i. is associated with the development of a neutrophil inflammatory response in perivascular regions and in the CNS parenchyma. Infiltration of neutrophils into the CNS was preceded by increased expression of tumor necrosis factor alpha and the neutrophil-attracting chemokine N51/KC within the CNS. Depletion of neutrophils with a cytotoxic monoclonal antibody (RB6-8C5) resulted in prolonged survival and decreased mortality in MVE-infected mice. In addition, neutrophil infiltration and disease onset correlated with expression of the enzyme-inducible nitric oxide synthase (iNOS) within the CNS. Inhibition of iNOS by aminoguanidine resulted in prolonged survival and decreased mortality in MVE-infected mice. This study provides strong support for the hypothesis that Murray Valley encephalitis is primarily an immunopathological disease.

* Corresponding author. Mailing address: Department of Microbiology, Princess Margaret Hospital for Children, GPO Box D184, Perth, WA 6001, Australia. Phone: 61 8 9340 8275. Fax: 61 8 9380 4474. E-mail: peter.mcminn{at}health.wa.gov.au.

Journal of Virology, October 1999, p. 8781-8790, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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