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Title: IRF3 polymorphisms induce different innate anti-Theiler's virus immune responses in RAW264.7 macrophages

Abstract

Persistent viral infections can lead to disease such as myocarditis. Theiler's murine encephalomyelitis virus (TMEV) infects macrophages of SJL/J (H-2s) mice establishing persistent infections leading to demyelinating disease. In contrast macrophages from B10.S (H-2s) mice clear TMEV. Activation of the transcription factor IRF3 induces IFN{beta}, ISG56, and apoptosis for viral clearance, but also inflammatory cytokines, such as IL-23 and IL6, which contribute to disease. Here we identify polymorphisms in the IRF3 of SJL/J versus B10.S mice that are located in DNA binding, nuclear localization, and autoinhibitory domains. SJL-IRF3 expression in RAW264.7 macrophage cells with or without TMEV infection decreased IL-23p19 promoter activity compared with B10S-IRF3. In contrast SJL-IRF3 increased IL-6, ISG56 and IFN{beta} in response to TMEV. B10S-IRF3 expression augmented apoptotic caspase activation and decreased viral RNA in TMEV-infected macrophages while SJL-IRF3 increased viral replication with less caspase activation. Therefore IRF3 polymorphisms contribute to viral persistence and altered cytokine expression.

Authors:
 [1];  [2];  [1];  [3];  [4];  [3]
  1. School of Biological Sciences, University of Nebraska Lincoln (United States)
  2. Endodontics, University of Nebraska Medical Center (United States)
  3. (United States)
  4. Nebraska Center for Virology, University of Nebraska Lincoln (United States)
Publication Date:
OSTI Identifier:
21587890
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 418; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2011.06.028; PII: S0042-6822(11)00297-2; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; DISEASES; DNA; INFLAMMATION; LYMPHOKINES; MACROPHAGES; MICE; RNA; TRANSCRIPTION FACTORS; VIRUSES; ANIMAL CELLS; ANIMALS; CONNECTIVE TISSUE CELLS; GROWTH FACTORS; MAMMALS; MICROORGANISMS; MITOGENS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PARASITES; PATHOLOGICAL CHANGES; PHAGOCYTES; PROTEINS; RODENTS; SOMATIC CELLS; SYMPTOMS; VERTEBRATES

Citation Formats

Moore, Tyler C., Al-Salleeh, Fahd M., Brown, Deborah M., Nebraska Center for Virology, University of Nebraska Lincoln, Petro, Thomas M., E-mail: tpetro@unmc.edu, and Departments of Oral Biology, University of Nebraska Medical Center. IRF3 polymorphisms induce different innate anti-Theiler's virus immune responses in RAW264.7 macrophages. United States: N. p., 2011. Web. doi:10.1016/j.virol.2011.06.028.
Moore, Tyler C., Al-Salleeh, Fahd M., Brown, Deborah M., Nebraska Center for Virology, University of Nebraska Lincoln, Petro, Thomas M., E-mail: tpetro@unmc.edu, & Departments of Oral Biology, University of Nebraska Medical Center. IRF3 polymorphisms induce different innate anti-Theiler's virus immune responses in RAW264.7 macrophages. United States. doi:10.1016/j.virol.2011.06.028.
Moore, Tyler C., Al-Salleeh, Fahd M., Brown, Deborah M., Nebraska Center for Virology, University of Nebraska Lincoln, Petro, Thomas M., E-mail: tpetro@unmc.edu, and Departments of Oral Biology, University of Nebraska Medical Center. Thu . "IRF3 polymorphisms induce different innate anti-Theiler's virus immune responses in RAW264.7 macrophages". United States. doi:10.1016/j.virol.2011.06.028.
@article{osti_21587890,
title = {IRF3 polymorphisms induce different innate anti-Theiler's virus immune responses in RAW264.7 macrophages},
author = {Moore, Tyler C. and Al-Salleeh, Fahd M. and Brown, Deborah M. and Nebraska Center for Virology, University of Nebraska Lincoln and Petro, Thomas M., E-mail: tpetro@unmc.edu and Departments of Oral Biology, University of Nebraska Medical Center},
abstractNote = {Persistent viral infections can lead to disease such as myocarditis. Theiler's murine encephalomyelitis virus (TMEV) infects macrophages of SJL/J (H-2s) mice establishing persistent infections leading to demyelinating disease. In contrast macrophages from B10.S (H-2s) mice clear TMEV. Activation of the transcription factor IRF3 induces IFN{beta}, ISG56, and apoptosis for viral clearance, but also inflammatory cytokines, such as IL-23 and IL6, which contribute to disease. Here we identify polymorphisms in the IRF3 of SJL/J versus B10.S mice that are located in DNA binding, nuclear localization, and autoinhibitory domains. SJL-IRF3 expression in RAW264.7 macrophage cells with or without TMEV infection decreased IL-23p19 promoter activity compared with B10S-IRF3. In contrast SJL-IRF3 increased IL-6, ISG56 and IFN{beta} in response to TMEV. B10S-IRF3 expression augmented apoptotic caspase activation and decreased viral RNA in TMEV-infected macrophages while SJL-IRF3 increased viral replication with less caspase activation. Therefore IRF3 polymorphisms contribute to viral persistence and altered cytokine expression.},
doi = {10.1016/j.virol.2011.06.028},
journal = {Virology},
issn = {0042-6822},
number = 1,
volume = 418,
place = {United States},
year = {2011},
month = {9}
}