Controllable and uncontrollable stress differentially impact pathogenicity and survival in a mouse model of viral encephalitis

J Neuroimmunol. 2018 Jun 15:319:130-141. doi: 10.1016/j.jneuroim.2018.02.014. Epub 2018 Mar 8.


Intranasal instillation of vesicular stomatitis virus (VSV) into mice given controllable stress (modeled by escapable foot shock, ES) resulted in enhanced pathogenicity and decreased survival relative to infected mice given uncontrollable stress (modeled by inescapable foot shock, IS) and non-shocked control mice. Survival likely reflected differential cytokine gene expression that may have been regulated by miR146a, a predicted stress-responsive upstream regulator. Controllability also enhanced the accumulation of brain T resident memory cells that persisted long after viral clearance. The unexpected facilitatory effect of ES on antiviral neuroimmune responses and pathogenicity may arise from differential immunoactivating and immunosuppressive effects of uncontrollable and controllable stress.

Keywords: Cytokine; Innate immunity; MicroRNA; Neuroinflammation; Stressor controllability; Vesicular stomatitis virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Encephalitis, Viral / immunology*
  • Helplessness, Learned*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Stress, Psychological / immunology*
  • Vesiculovirus