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STING induces early IFN-β in the liver and constrains myeloid cell-mediated dissemination of murine cytomegalovirus.
- Source :
-
Nature communications [Nat Commun] 2019 Jun 27; Vol. 10 (1), pp. 2830. Date of Electronic Publication: 2019 Jun 27. - Publication Year :
- 2019
-
Abstract
- Cytomegalovirus is a DNA-encoded β-herpesvirus that induces STING-dependent type 1 interferon responses in macrophages and uses myeloid cells as a vehicle for dissemination. Here we report that STING knockout mice are as resistant to murine cytomegalovirus (MCMV) infection as wild-type controls, whereas mice with a combined Toll-like receptor/RIG-I-like receptor/STING signaling deficiency do not mount type 1 interferon responses and succumb to the infection. Although STING alone is dispensable for survival, early IFN-β induction in Kupffer cells is STING-dependent and controls early hepatic virus propagation. Infection experiments with an inducible reporter MCMV show that STING constrains MCMV replication in myeloid cells and limits viral dissemination via these cells. By contrast, restriction of viral dissemination from hepatocytes to other organs is independent of STING. Thus, during MCMV infection STING is involved in early IFN-β induction in Kupffer cells and the restriction of viral dissemination via myeloid cells, whereas it is dispensable for survival.
- Subjects :
- Animals
Female
Hepatocytes metabolism
Hepatocytes virology
Herpesviridae Infections virology
Host-Pathogen Interactions
Interferon-beta genetics
Kupffer Cells metabolism
Kupffer Cells virology
Liver virology
Male
Membrane Proteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Muromegalovirus genetics
Myeloid Cells virology
Rodent Diseases genetics
Rodent Diseases virology
Signal Transduction
Toll-Like Receptors genetics
Toll-Like Receptors metabolism
Herpesviridae Infections veterinary
Interferon-beta metabolism
Liver metabolism
Membrane Proteins metabolism
Muromegalovirus physiology
Myeloid Cells metabolism
Rodent Diseases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31249303
- Full Text :
- https://doi.org/10.1038/s41467-019-10863-0