title: A distinct brain pathway links viral RNA exposure to sickness behavior.
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.
authors.affiliation: Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Pete R
authors.initials: PR
authors.lastname: Levasseur
authors.affiliation: Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR 97239, USA.|MD/PhD Program, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Michaelis
authors.affiliation: Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR 97239, USA.|MD/PhD Program, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Burfeind
authors.affiliation: Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR 97239, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Marks
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001831:Body Temperature; D001921:Brain / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D006801:Humans; D055809:Illness Behavior; D007249:Inflammation / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D011788:Quality of Life; D012330:RNA, Double-Stranded / Q000008:administration & dosage / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D053594:Myeloid Differentiation Factor 88; D012330:RNA, Double-Stranded; D012367:RNA, Viral