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Publication : ATF3 regulates MCMV infection in mice by modulating IFN-gamma expression in natural killer cells.

First Author  Rosenberger CM Year  2008
Journal  Proc Natl Acad Sci U S A Volume  105
Issue  7 Pages  2544-9
PubMed ID  18268321 Mgi Jnum  J:132172
Mgi Id  MGI:3775345 Doi  10.1073/pnas.0712182105
Citation  Rosenberger CM, et al. (2008) ATF3 regulates MCMV infection in mice by modulating IFN-gamma expression in natural killer cells. Proc Natl Acad Sci U S A 105(7):2544-9
abstractText  Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3-deficient mice are more susceptible to endotoxic shock. Here, we demonstrate that ATF3 interacts with a cis-regulatory element of the IFN-gamma gene in natural killer (NK) cells, and that ATF3null NK cells show increased transcription and secretion of IFN-gamma. NK cell-derived IFN-gamma has previously been demonstrated to be protective against murine cytomegalovirus (MCMV) infection, and we show here that ATF3null mice exhibit decreased hepatic viral load and reduced liver histopathology upon challenge with MCMV. Reconstitution of NK-deficient mice with ATF3null NK cells more effectively controlled MCMV infection than mice reconstituted with WT cells, indicating that ATF3 acts within NK cells to regulate antiviral responses.
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