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Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors

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Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors. / Horan, Kristy A.; Hansen, Kathrine; Jakobsen, Martin R.; Holm, Christian K.; Søby, Stine; Unterholzner, Leonie; Thompson, Mikayla; West, John A.; Iversen, Marie B.; Rasmussen, Simon B.; Ellermann-Eriksen, Svend; Kurt-Jones, Evelyn; Landolfo, Santo; Damania, Blossom; Melchjorsen, Jesper; Bowie, Andrew G.; Fitzgerald, Katherine A.; Paludan, Søren R.

In: Journal of Immunology, Vol. 190, No. 5, 01.03.2013, p. 2311-2319.

Research output: Contribution to journalJournal article

Harvard

Horan, KA, Hansen, K, Jakobsen, MR, Holm, CK, Søby, S, Unterholzner, L, Thompson, M, West, JA, Iversen, MB, Rasmussen, SB, Ellermann-Eriksen, S, Kurt-Jones, E, Landolfo, S, Damania, B, Melchjorsen, J, Bowie, AG, Fitzgerald, KA & Paludan, SR 2013, 'Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors', Journal of Immunology, vol. 190, no. 5, pp. 2311-2319. https://doi.org/10.4049/jimmunol.1202749

APA

Horan, K. A., Hansen, K., Jakobsen, M. R., Holm, C. K., Søby, S., Unterholzner, L., Thompson, M., West, J. A., Iversen, M. B., Rasmussen, S. B., Ellermann-Eriksen, S., Kurt-Jones, E., Landolfo, S., Damania, B., Melchjorsen, J., Bowie, A. G., Fitzgerald, K. A., & Paludan, S. R. (2013). Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors. Journal of Immunology, 190(5), 2311-2319. https://doi.org/10.4049/jimmunol.1202749

Vancouver

Author

Horan, Kristy A. ; Hansen, Kathrine ; Jakobsen, Martin R. ; Holm, Christian K. ; Søby, Stine ; Unterholzner, Leonie ; Thompson, Mikayla ; West, John A. ; Iversen, Marie B. ; Rasmussen, Simon B. ; Ellermann-Eriksen, Svend ; Kurt-Jones, Evelyn ; Landolfo, Santo ; Damania, Blossom ; Melchjorsen, Jesper ; Bowie, Andrew G. ; Fitzgerald, Katherine A. ; Paludan, Søren R. / Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors. In: Journal of Immunology. 2013 ; Vol. 190, No. 5. pp. 2311-2319.

Bibtex

@article{0afcc9dad8e84f81a8acca0eda4acef9,
title = "Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors",
abstract = "The innate immune system is important for control of infections, including herpesvirus infections. Intracellular DNA potently stimulates antiviral IFN responses. It is known that plasmacytoid dendritic cells sense herpesvirus DNA in endosomes via TLR9 and that nonimmune tissue cells can sense herpesvirus DNA in the nucleus. However, it remains unknown how and where myeloid cells, such as macrophages and conventional dendritic cells, detect infections with herpesviruses. In this study, we demonstrate that the HSV-1 capsid was ubiquitinated in the cytosol and degraded by the proteasome, hence releasing genomic DNA into the cytoplasm for detection by DNA sensors. In this context, the DNA sensor IFN-γ-inducible 16 is important for induction of IFN-β in human macrophages postinfection with HSV-1 and CMV. Viral DNA localized to the same cytoplasmic regions as did IFN-γ-inducible 16, with DNA sensing being independent of viral nuclear entry. Thus, proteasomal degradation of herpesvirus capsids releases DNA to the cytoplasm for recognition by DNA sensors.",
keywords = "Animals, Capsid, Cell Line, Cell Nucleus, Cercopithecus aethiops, Cytomegalovirus, Cytosol, DNA, Viral, Dendritic Cells, Gene Silencing, Herpesvirus 1, Human, Humans, Interferon-beta, Macrophages, Nuclear Proteins, Phosphoproteins, Proteasome Endopeptidase Complex, RNA, Small Interfering, Ubiquitination, Vero Cells",
author = "Horan, {Kristy A.} and Kathrine Hansen and Jakobsen, {Martin R.} and Holm, {Christian K.} and Stine S{\o}by and Leonie Unterholzner and Mikayla Thompson and West, {John A.} and Iversen, {Marie B.} and Rasmussen, {Simon B.} and Svend Ellermann-Eriksen and Evelyn Kurt-Jones and Santo Landolfo and Blossom Damania and Jesper Melchjorsen and Bowie, {Andrew G.} and Fitzgerald, {Katherine A.} and Paludan, {S{\o}ren R.}",
year = "2013",
month = mar,
day = "1",
doi = "10.4049/jimmunol.1202749",
language = "English",
volume = "190",
pages = "2311--2319",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

RIS

TY - JOUR

T1 - Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors

AU - Horan, Kristy A.

AU - Hansen, Kathrine

AU - Jakobsen, Martin R.

AU - Holm, Christian K.

AU - Søby, Stine

AU - Unterholzner, Leonie

AU - Thompson, Mikayla

AU - West, John A.

AU - Iversen, Marie B.

AU - Rasmussen, Simon B.

AU - Ellermann-Eriksen, Svend

AU - Kurt-Jones, Evelyn

AU - Landolfo, Santo

AU - Damania, Blossom

AU - Melchjorsen, Jesper

AU - Bowie, Andrew G.

AU - Fitzgerald, Katherine A.

AU - Paludan, Søren R.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - The innate immune system is important for control of infections, including herpesvirus infections. Intracellular DNA potently stimulates antiviral IFN responses. It is known that plasmacytoid dendritic cells sense herpesvirus DNA in endosomes via TLR9 and that nonimmune tissue cells can sense herpesvirus DNA in the nucleus. However, it remains unknown how and where myeloid cells, such as macrophages and conventional dendritic cells, detect infections with herpesviruses. In this study, we demonstrate that the HSV-1 capsid was ubiquitinated in the cytosol and degraded by the proteasome, hence releasing genomic DNA into the cytoplasm for detection by DNA sensors. In this context, the DNA sensor IFN-γ-inducible 16 is important for induction of IFN-β in human macrophages postinfection with HSV-1 and CMV. Viral DNA localized to the same cytoplasmic regions as did IFN-γ-inducible 16, with DNA sensing being independent of viral nuclear entry. Thus, proteasomal degradation of herpesvirus capsids releases DNA to the cytoplasm for recognition by DNA sensors.

AB - The innate immune system is important for control of infections, including herpesvirus infections. Intracellular DNA potently stimulates antiviral IFN responses. It is known that plasmacytoid dendritic cells sense herpesvirus DNA in endosomes via TLR9 and that nonimmune tissue cells can sense herpesvirus DNA in the nucleus. However, it remains unknown how and where myeloid cells, such as macrophages and conventional dendritic cells, detect infections with herpesviruses. In this study, we demonstrate that the HSV-1 capsid was ubiquitinated in the cytosol and degraded by the proteasome, hence releasing genomic DNA into the cytoplasm for detection by DNA sensors. In this context, the DNA sensor IFN-γ-inducible 16 is important for induction of IFN-β in human macrophages postinfection with HSV-1 and CMV. Viral DNA localized to the same cytoplasmic regions as did IFN-γ-inducible 16, with DNA sensing being independent of viral nuclear entry. Thus, proteasomal degradation of herpesvirus capsids releases DNA to the cytoplasm for recognition by DNA sensors.

KW - Animals

KW - Capsid

KW - Cell Line

KW - Cell Nucleus

KW - Cercopithecus aethiops

KW - Cytomegalovirus

KW - Cytosol

KW - DNA, Viral

KW - Dendritic Cells

KW - Gene Silencing

KW - Herpesvirus 1, Human

KW - Humans

KW - Interferon-beta

KW - Macrophages

KW - Nuclear Proteins

KW - Phosphoproteins

KW - Proteasome Endopeptidase Complex

KW - RNA, Small Interfering

KW - Ubiquitination

KW - Vero Cells

U2 - 10.4049/jimmunol.1202749

DO - 10.4049/jimmunol.1202749

M3 - Journal article

C2 - 23345332

VL - 190

SP - 2311

EP - 2319

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -