author_facet Ge, Yi
Mansell, Ashley
Ussher, James E.
Brooks, Anna E. S.
Manning, Kristy
Wang, Carol J. H.
Taylor, John A.
Ge, Yi
Mansell, Ashley
Ussher, James E.
Brooks, Anna E. S.
Manning, Kristy
Wang, Carol J. H.
Taylor, John A.
author Ge, Yi
Mansell, Ashley
Ussher, James E.
Brooks, Anna E. S.
Manning, Kristy
Wang, Carol J. H.
Taylor, John A.
spellingShingle Ge, Yi
Mansell, Ashley
Ussher, James E.
Brooks, Anna E. S.
Manning, Kristy
Wang, Carol J. H.
Taylor, John A.
Journal of Virology
Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
Virology
Insect Science
Immunology
Microbiology
author_sort ge, yi
spelling Ge, Yi Mansell, Ashley Ussher, James E. Brooks, Anna E. S. Manning, Kristy Wang, Carol J. H. Taylor, John A. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.03099-12 <jats:title>ABSTRACT</jats:title> <jats:p> Nonstructural protein 4 (NSP4), encoded by rotavirus, exhibits various properties linked to viral pathogenesis, including enterotoxic activity. A recent study (O. V. Kavanagh et al., Vaccine 28:3106-3111, 2010) indicated that NSP4 also has adjuvant properties, suggesting a possible role in the innate immune response to rotavirus infection. We report here that NSP4 purified from the medium of rotavirus-infected Caco-2 cells triggers the secretion of proinflammatory cytokines from macrophage-like THP-1 cells and nitric oxide from murine RAW 264.7 cells. Secretion is accompanied by the stimulation of p38 and JNK mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB. NSP4 triggered the secretion of cytokines from murine macrophages derived from wild-type but not MyD88 <jats:sup>−/−</jats:sup> or Toll-like receptor 2 (TLR2 <jats:sup>−/−</jats:sup> ) mice and induced secretion of interleukin-8 (IL-8) from human embryonic kidney cells transfected with TLR2 but not TLR4. Our studies identify NSP4 as a pathogen-associated molecular pattern (PAMP) encoded by rotavirus and provide a mechanism for the production of proinflammatory cytokines associated with the clinical symptoms of infection in humans and animals. </jats:p> Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2 Journal of Virology
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title Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_unstemmed Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_full Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_fullStr Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_full_unstemmed Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_short Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_sort rotavirus nsp4 triggers secretion of proinflammatory cytokines from macrophages via toll-like receptor 2
topic Virology
Insect Science
Immunology
Microbiology
url http://dx.doi.org/10.1128/jvi.03099-12
publishDate 2013
physical 11160-11167
description <jats:title>ABSTRACT</jats:title> <jats:p> Nonstructural protein 4 (NSP4), encoded by rotavirus, exhibits various properties linked to viral pathogenesis, including enterotoxic activity. A recent study (O. V. Kavanagh et al., Vaccine 28:3106-3111, 2010) indicated that NSP4 also has adjuvant properties, suggesting a possible role in the innate immune response to rotavirus infection. We report here that NSP4 purified from the medium of rotavirus-infected Caco-2 cells triggers the secretion of proinflammatory cytokines from macrophage-like THP-1 cells and nitric oxide from murine RAW 264.7 cells. Secretion is accompanied by the stimulation of p38 and JNK mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB. NSP4 triggered the secretion of cytokines from murine macrophages derived from wild-type but not MyD88 <jats:sup>−/−</jats:sup> or Toll-like receptor 2 (TLR2 <jats:sup>−/−</jats:sup> ) mice and induced secretion of interleukin-8 (IL-8) from human embryonic kidney cells transfected with TLR2 but not TLR4. Our studies identify NSP4 as a pathogen-associated molecular pattern (PAMP) encoded by rotavirus and provide a mechanism for the production of proinflammatory cytokines associated with the clinical symptoms of infection in humans and animals. </jats:p>
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author Ge, Yi, Mansell, Ashley, Ussher, James E., Brooks, Anna E. S., Manning, Kristy, Wang, Carol J. H., Taylor, John A.
author_facet Ge, Yi, Mansell, Ashley, Ussher, James E., Brooks, Anna E. S., Manning, Kristy, Wang, Carol J. H., Taylor, John A., Ge, Yi, Mansell, Ashley, Ussher, James E., Brooks, Anna E. S., Manning, Kristy, Wang, Carol J. H., Taylor, John A.
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container_issue 20
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description <jats:title>ABSTRACT</jats:title> <jats:p> Nonstructural protein 4 (NSP4), encoded by rotavirus, exhibits various properties linked to viral pathogenesis, including enterotoxic activity. A recent study (O. V. Kavanagh et al., Vaccine 28:3106-3111, 2010) indicated that NSP4 also has adjuvant properties, suggesting a possible role in the innate immune response to rotavirus infection. We report here that NSP4 purified from the medium of rotavirus-infected Caco-2 cells triggers the secretion of proinflammatory cytokines from macrophage-like THP-1 cells and nitric oxide from murine RAW 264.7 cells. Secretion is accompanied by the stimulation of p38 and JNK mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB. NSP4 triggered the secretion of cytokines from murine macrophages derived from wild-type but not MyD88 <jats:sup>−/−</jats:sup> or Toll-like receptor 2 (TLR2 <jats:sup>−/−</jats:sup> ) mice and induced secretion of interleukin-8 (IL-8) from human embryonic kidney cells transfected with TLR2 but not TLR4. Our studies identify NSP4 as a pathogen-associated molecular pattern (PAMP) encoded by rotavirus and provide a mechanism for the production of proinflammatory cytokines associated with the clinical symptoms of infection in humans and animals. </jats:p>
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spelling Ge, Yi Mansell, Ashley Ussher, James E. Brooks, Anna E. S. Manning, Kristy Wang, Carol J. H. Taylor, John A. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.03099-12 <jats:title>ABSTRACT</jats:title> <jats:p> Nonstructural protein 4 (NSP4), encoded by rotavirus, exhibits various properties linked to viral pathogenesis, including enterotoxic activity. A recent study (O. V. Kavanagh et al., Vaccine 28:3106-3111, 2010) indicated that NSP4 also has adjuvant properties, suggesting a possible role in the innate immune response to rotavirus infection. We report here that NSP4 purified from the medium of rotavirus-infected Caco-2 cells triggers the secretion of proinflammatory cytokines from macrophage-like THP-1 cells and nitric oxide from murine RAW 264.7 cells. Secretion is accompanied by the stimulation of p38 and JNK mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB. NSP4 triggered the secretion of cytokines from murine macrophages derived from wild-type but not MyD88 <jats:sup>−/−</jats:sup> or Toll-like receptor 2 (TLR2 <jats:sup>−/−</jats:sup> ) mice and induced secretion of interleukin-8 (IL-8) from human embryonic kidney cells transfected with TLR2 but not TLR4. Our studies identify NSP4 as a pathogen-associated molecular pattern (PAMP) encoded by rotavirus and provide a mechanism for the production of proinflammatory cytokines associated with the clinical symptoms of infection in humans and animals. </jats:p> Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2 Journal of Virology
spellingShingle Ge, Yi, Mansell, Ashley, Ussher, James E., Brooks, Anna E. S., Manning, Kristy, Wang, Carol J. H., Taylor, John A., Journal of Virology, Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2, Virology, Insect Science, Immunology, Microbiology
title Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_full Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_fullStr Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_full_unstemmed Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_short Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
title_sort rotavirus nsp4 triggers secretion of proinflammatory cytokines from macrophages via toll-like receptor 2
title_unstemmed Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
topic Virology, Insect Science, Immunology, Microbiology
url http://dx.doi.org/10.1128/jvi.03099-12