A distinct brain pathway links viral RNA exposure to sickness behavior

Xinxia Zhu, Pete R. Levasseur, Katherine A. Michaelis, Kevin G. Burfeind, Daniel L. Marks

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Sickness behaviors and metabolic responses to invading pathogens are common to nearly all types of infection. These responses evolved to provide short-term benefit to the host to ward off infection, but impact on quality of life, and when prolonged lead to neurodegeneration, depression, and cachexia. Among the major infectious agents, viruses most frequently enter the brain, resulting in profound neuroinflammation. We sought to define the unique features of the inflammatory response in the brain to these infections. We demonstrate that the molecular pathway defining the central response to dsRNA is distinct from that found in the periphery. The behavioral and physical response to the dsRNA mimetic poly I:C is dependent on signaling via MyD88 when it is delivered centrally, whereas this response is mediated via the TRIF pathway when delivered peripherally. We also define the likely cellular candidates for this MyD88-dependent step. These findings suggest that symptom management is possible without ameliorating protective antiviral immune responses.

Original languageEnglish (US)
Article number29885
JournalScientific Reports
Volume6
DOIs
StatePublished - Jul 20 2016

ASJC Scopus subject areas

  • General

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