| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Pisitkun, Prapaporn Jorgensen, Joan P. Hansen, Kathrine Adler, Heiko Schattgen, Stefan A. O'Hare, Peter Ploegh, Hidde L. Sun, Ren Upton, Jason W. West, John A. Damania, Blossom Wang, Lucas J. Horan, Kristy A. Hilterbrand, Adam T. Jakobsen, Martin R. Paludan, Søren R. Sun, Chenglong Fitzgerald, Katherine A. |
| Description |
Author Affiliation: Sun C ( Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark); Schattgen SA ( Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655); Pisitkun P ( Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark); Jorgensen JP ( Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark); Hilterbrand AT ( Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712); Wang LJ ( Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712); West JA ( Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599); Hansen K ( Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark); Horan KA ( Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark); Jakobsen MR ( Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark); O'Hare P ( Section of Virology, Faculty of Medicine, Imperial College, St. Mary's Campus, London W2 1PG, United Kingdom); Adler H ( Helmholtz Zentrum Munich, German Research Center for Environmental Health, D-81377 Munich, Germany); Sun R ( Department of Molecular Biology and Medical Pharmacology, Faculty of Medicine, University of California, Los Angeles, Los Angeles, CA 90095); Ploegh HL ( Whitehead Institute for Biomedical Research, Cambridge, MA 02142.); Damania B ( Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599); Upton JW ( Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712); Fitzgerald KA ( Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655); Paludan SR ( Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark) |
| Abstract |
Herpesviruses are DNA viruses harboring the capacity to establish lifelong latent-recurrent infections. There is limited knowledge about viruses targeting the innate DNA-sensing pathway, as well as how the innate system impacts on the latent reservoir of herpesvirus infections. In this article, we report that murine gammaherpesvirus 68 (MHV68), in contrast to - and ß-herpesviruses, induces very limited innate immune responses through DNA-stimulated pathways, which correspondingly played only a minor role in the control of MHV68 infections in vivo. Similarly, Kaposi's sarcoma-associated herpesvirus also did not stimulate immune signaling through the DNA-sensing pathways. Interestingly, an MHV68 mutant lacking deubiquitinase (DUB) activity, embedded within the large tegument protein open reading frame (ORF)64, gained the capacity to stimulate the DNA-activated stimulator of IFN genes (STING) pathway. We found that ORF64 targeted a step in the DNA-activated pathways upstream of the bifurcation into the STING and absent in melanoma 2 pathways, and lack of the ORF64 DUB was associated with impaired delivery of viral DNA to the nucleus, which, instead, localized to the cytoplasm. Correspondingly, the ORF64 DUB active site mutant virus exhibited impaired ability to establish latent infection in wild-type, but not STING-deficient, mice. Thus, gammaherpesviruses evade immune activation by the cytosolic DNA-sensing pathway, which, in the MHV68 model, facilitates establishment of infections. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1402495 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-02-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Dna, Viral Immunology Gammaherpesvirinae Herpesviridae Infections Immunity, Innate Virus Latency Animals Cytosol Disease Models, Animal Enzyme-linked Immunosorbent Assay Flow Cytometry Macrophages Virology Mice Mice, Inbred C57bl Mice, Knockout Microscopy, Confocal Real-time Polymerase Chain Reaction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
