Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection
The 3β-hydroxysteroid dehydrogenase (3β-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Vaccinia virus (VV) also synthesizes steroid hormones with a 3β-HSD enzyme (v3β-HSD) encoded by gene A44L. Here we examined the effects of v3β-HSD in VV disease using wild-type (vA44L), del...
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The Rockefeller University Press
2003
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193778/ |
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pubmed-21937782008-04-11 Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection Reading, Patrick C. Moore, Jeffrey B. Smith, Geoffrey L. Article The 3β-hydroxysteroid dehydrogenase (3β-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Vaccinia virus (VV) also synthesizes steroid hormones with a 3β-HSD enzyme (v3β-HSD) encoded by gene A44L. Here we examined the effects of v3β-HSD in VV disease using wild-type (vA44L), deletion (vΔA44L), 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 vΔA44L or control viruses the only difference observed between groups was the reduced corticosterone level in lungs and plasma of vΔA44L-infected animals. Other parameters examined (body weight, signs of illness, temperature, virus titres, the pulmonary inflammatory infiltrate, and interferon [IFN]-γ levels) were indistinguishable between groups. Subsequently, vΔA44L-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-γ production and augmented cytotoxic T lymphocyte activity. These data suggest that steroid production by v3β-HSD contributes to virus virulence by inhibiting an effective inflammatory response to infection. The Rockefeller University Press 2003-05-19 /pmc/articles/PMC2193778/ /pubmed/12756265 http://dx.doi.org/10.1084/jem.20022201 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Reading, Patrick C. Moore, Jeffrey B. Smith, Geoffrey L. |
| spellingShingle |
Reading, Patrick C. Moore, Jeffrey B. Smith, Geoffrey L. Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection |
| author_facet |
Reading, Patrick C. Moore, Jeffrey B. Smith, Geoffrey L. |
| author_sort |
Reading, Patrick C. |
| title |
Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection |
| title_short |
Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection |
| title_full |
Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection |
| title_fullStr |
Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection |
| title_full_unstemmed |
Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection |
| title_sort |
steroid hormone synthesis by vaccinia virus suppresses the inflammatory response to infection |
| description |
The 3β-hydroxysteroid dehydrogenase (3β-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Vaccinia virus (VV) also synthesizes steroid hormones with a 3β-HSD enzyme (v3β-HSD) encoded by gene A44L. Here we examined the effects of v3β-HSD in VV disease using wild-type (vA44L), deletion (vΔA44L), 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 vΔA44L or control viruses the only difference observed between groups was the reduced corticosterone level in lungs and plasma of vΔA44L-infected animals. Other parameters examined (body weight, signs of illness, temperature, virus titres, the pulmonary inflammatory infiltrate, and interferon [IFN]-γ levels) were indistinguishable between groups. Subsequently, vΔA44L-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-γ production and augmented cytotoxic T lymphocyte activity. These data suggest that steroid production by v3β-HSD contributes to virus virulence by inhibiting an effective inflammatory response to infection. |
| publisher |
The Rockefeller University Press |
| publishDate |
2003 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193778/ |
| _version_ |
1611431296944308224 |