mortality/aging
• mice show lower survival rate after herpes simplex virus type 1 (HSV-1, KOS strain)
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immune system
• innate immune responses triggered by cyclic GMP-AMP (cGAMP) are decreased in BMDMs
• innate immune responses against DNA viruses or exogenous cytosolic DNA are impaired in BMDMs and PMs
• BMDMs and PMs show reduced production of Ifnb, IL-6, Cxcl10 and Ifit1 in response to stimulation with exogenous cytosolic DNA, including HSV60, VACV70 (a 70 bp dsDNA oligonucleotide containing vaccinia virus motifs), HT DNA and the cytosolic DNA-analog poly (dA:dT), and BMDMs show inhibited production of IFN-beta, TNF-alpha, and IL-6 upon stimulation with HSV-1, HSV60, VACV70, poly(dA:dT), or HT DNA
• following transfection with HSV60, IFN-stimulatory DNA, VACV70, or HT DNA, PMs show decreased production of Ifnb and Il-6
• MEFs show impaired DNA virus or exogenous cytosolic DNA-triggered innate immune responses; MEFs infected with HSV-1 show an increase in HSV-1 infection, lower levels of Ifnb, Il-6, Ccl5, and Ifit1 mRNA expression, inhibited secretion of IFN-beta, IL-6 and TNF-alpha, MEFs stimulated with exogenous cytosolic DNA show inhibited secretion of IFN-beta, IL-6 and TNF-alpha, MEFs transfected with HSV60 show lower levels of Ifnb, Il-6, Ccl5, and Ifit1 mRNA expression, and MEFs incubated with culture supernatants from HSV60 transfected mutant BMDMs show more HSV-1 infection, indicating impaired antiviral immune responses upon HSV60 transfection
• however, no differences in MEFs are seen in the innate immune responses against RNA virus or cytosolic RNA
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• mice show greater body weight loss, more severe destruction of the lungs, decreased antiviral immune responses and lower survival rate after HSV-1 infection
• mice show reduced production of Ifnb, Cxcl10, Ifit1, and Il-6 and elevated genomic DNA copies of HSV-1 in the lung, liver, and spleen 24 hours after HSV-1 infection
• mice infected with HSV-1 show impaired antiviral responses and enhanced HSV-1 in the brain 4 days after infection
• mice intranasally infected with HSV-1 for 24 hours show reduced secretion of IFN-beta, TNF-alpha, and IL-6 in the BALF
• bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) show an increase in HSV-1 infection, with reduced production of Ifnb, IL-6, Cxcl10 and Ifit1
• PMs show inhibited secretion of IFN-beta and TNF-alpha in response to HSV-1 infection
• however, RNA virus- or cytosolic RNA-triggered innate immune responses are not affected and
mice do not show differences from controls in body weight loss, production of IFN-beta, proinflammatory cytokines, and antiviral proteins in liver, lung, spleen, serum, or BALFs after vesicular stomatitis virus (VSV) infection and no differences in IFN-beta and IL-6 secretion after Sendai virus (SeV) infection
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• mice show lower survival rate after herpes simplex virus type 1 (HSV-1, KOS strain)
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