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Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection

Patrick C. Reading, Jeffrey B. Moore and Geoffrey L. Smith

Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, London W2 1PG, United Kingdom

Address correspondence to Geoffrey L. Smith, Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK. Phone: 207-594-3972; Fax: 207-594-3973; E-mail: glsmith{at}ic.ac.uk

The 3ß-hydroxysteroid dehydrogenase (3ß-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Vaccinia virus (VV) also synthesizes steroid hormones with a 3ß-HSD enzyme (v3ß-HSD) encoded by gene A44L. Here we examined the effects of v3ß-HSD in VV disease using wild-type (vA44L), deletion (vA44L), and revertant (vA44L-rev) viruses in a murine intranasal model. Loss of A44L was associated with an attenuated phenotype. Early (days 1–3) after infection with vA44L or control viruses the only difference observed between groups was the reduced corticosterone level in lungs and plasma of vA44L-infected animals. Other parameters examined (body weight, signs of illness, temperature, virus titres, the pulmonary inflammatory infiltrate, and interferon [IFN]- levels) were indistinguishable between groups. Subsequently, vA44L-infected animals had reduced weight loss and signs of illness, and displayed a vigorous pulmonary inflammatory response. This was characterized by rapid recruitment of CD4⁺ and CD8⁺ lymphocytes, enhanced IFN- production and augmented cytotoxic T lymphocyte activity. These data suggest that steroid production by v3ß-HSD contributes to virus virulence by inhibiting an effective inflammatory response to infection.

Key Words: NK cell • CTL • glucocorticoid • virulence • immunomodulation

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