ID: 241. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Ganesan, Priya; Bohn, Larissa; O'Donnell, Lauren A.
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 109
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.244
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">Viral infections in the central nervous system (CNS) are associated with devastating neurological consequences, particularly in newborns. Neonates are often unable to control viruses in the brain and suffer extensive neuronal loss, despite mounting an immune response. To study viral CNS infections, we use a transgenic mouse model of neuronally-restricted measles virus (MV) infection (NSE-CD46 mice), where the human isoform of CD46, a MV receptor, is expressed under the control of the neuron-specific enolase promoter. Adult CD46+ mice survive infection and clear MV in an interferon gamma (IFNg)- and T cell-dependent manner. Neonatal CD46 mice succumb by 15 days post infection (dpi) despite T cell infiltration. Neonatal mice lacking IFNg succumb more rapidly (100% mortality by 10 dpi) despite higher T cell infiltration and equivalent natural killer cell infiltration and microglial activation compared to CD46+ neonates. CD46+ adults show greater CD4 T cell infiltration compared to neonates, despite lower levels of virus in the brain. Quantitative RT-PCR analysis demonstrated expression of pro-inflammatory cytokine genes such as IFNg, IFN<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7p1c" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e61" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">α</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>2, IL-1<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7p1c" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e66" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">α</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>, IL1<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7qdz" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si3.gif" display="inline" overflow="scroll" id="d13e71" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>, IL-6, and TNF<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7p1c" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e77" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">α</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> in MV infected neonates, as well as the anti-inflammatory Interleukin 1 receptor antagonist. Current experiments aim to compare anti-viral cytokines protein levels between MV-infected adults and neonates. These results suggest the neonates are capable of significant immune cell infiltration and cytokine production, but that the cytokine milieu is ineffective at controlling MV. These findings further suggest that the T cell response may contribute to neuropathology, as lower T cell infiltration is associated with prolonged survival in neonates.</p> </sec> </abstract>