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O'Donnell LA , Conway S , Rose RW , Nicolas E , Slifker M , Balachandran S , Rall GF
STAT1-independent control of a neurotropic measles virus challenge in primary neurons and infected mice
Journal of Immunology. 2012 Feb 15;188(4) :1915-23
PMID: 22246627    PMCID: PMC3273675   
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Neurons are chiefly nonrenewable; thus, cytolytic immune strategies to clear or control neurotropic viral infections could have lasting neurologic consequences. IFN-gamma is a potent antiviral cytokine that is critical for noncytolytic clearance of multiple neurotropic viral infections, including measles virus (MV); however, the downstream pathways through which IFN-gamma functions in neurons have not been defined. Unlike affects gene expression via rapid and robust activation of STAT1, basal STAT1 levels in primary hippocampal neurons are constitutively low, resulting in attenuated STAT1 activation and consequently slower kinetics of IFN-gamma-driven STAT1-dependent gene expression. Given this altered expression and activation of STAT1 in neurons, we sought to determine whether STAT1 was required for IFN-gamma-mediated protection from infection in neurons. To do so, we evaluated the consequences of MV challenge of STAT1-deficient mice and primary hippocampal neurons explanted from these mice. Surprisingly, the absence of STAT1 did not restrict the ability of IFN-gamma to control viral infection either in vivo or ex vivo. Moreover, the canonical IFN-gamma-triggered STAT1 gene expression was not induced in STAT1-deficient neurons, suggesting that IFN-gamma regulates neuronal STAT1-independent pathways to control viral replication.
O'Donnell, Lauren A Conway, Stephen Rose, R Wesley Nicolas, Emmanuelle Slifker, Michael Balachandran, Siddharth Rall, Glenn F F32 NS062519-01/NS/NINDS NIH HHS/United States P30CA006927/CA/NCI NIH HHS/United States R01 NS40500/NS/NINDS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Journal of immunology (Baltimore, Md. : 1950) J Immunol. 2012 Feb 15;188(4):1915-23. Epub 2012 Jan 13.