Virus infection of the CNS disrupts the immune-neural-synaptic axis via induction of pleiotropic gene regulation of host responses

Elife. 2021 Feb 18:10:e62273. doi: 10.7554/eLife.62273.

Abstract

Treatment for many viral infections of the central nervous system (CNS) remains only supportive. Here we address a remaining gap in our knowledge regarding how the CNS and immune systems interact during viral infection. By examining the regulation of the immune and nervous system processes in a nonhuman primate model of West Nile virus neurological disease, we show that virus infection disrupts the homeostasis of the immune-neural-synaptic axis via induction of pleiotropic genes with distinct functions in each component of the axis. This pleiotropic gene regulation suggests an unintended off-target negative impact of virus-induced host immune responses on the neurotransmission, which may be a common feature of various viral infections of the CNS.

Keywords: functional genomics; immune system; immunology; infectious disease; inflammation; microbiology; neuronal system; pleiotropic genes; rhesus macaque; synapses; virus.

Publication types

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

MeSH terms

  • Adaptive Immunity / genetics*
  • Animals
  • Central Nervous System / immunology*
  • Disease Models, Animal
  • Female
  • Genetic Pleiotropy / immunology*
  • Immunity, Innate / genetics*
  • Macaca mulatta
  • Male
  • West Nile Fever / immunology*
  • West Nile Fever / virology
  • West Nile virus / physiology*

Associated data

  • GEO/GSE122798

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.