title: Metagenomic and metabolomic characterization of rabies encephalitis: new insights into the treatment of an ancient disease.
abstract: Rabies virus (RV) infection is a fatal nervous system disorder. We describe a patient who died of rabies despite a neuroprotective intervention. Neuropathology showed neuronal loss with abundant RV antigen, genome, and Negri bodies, accompanied by intense neuroinflammation, including by CD8(+) T lymphocyte infiltrates. Deep sequencing and real-time reverse-transcription polymerase chain reaction revealed RNA encoding a bat RV strain together with inflammatory gene induction. RV-infected brain demonstrated reduced neuronal metabolites with an anaerobic metabolic profile by nuclear magnetic resonance (NMR) spectroscopy. These multiplatform studies highlight the extent of ongoing viral replication coupled with inflammation in treated rabies, indicative of a neurological immune reconstitution inflammatory syndrome.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Reinke
authors.forename: Lothar
authors.initials: L
authors.lastname: Resch
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Maingat
authors.forename: William
authors.initials: W
authors.lastname: Branton
authors.forename: Alan C
authors.initials: AC
authors.lastname: Jackson
authors.forename: Robert
authors.initials: R
authors.lastname: Holt
authors.forename: Carolyn
authors.initials: C
authors.lastname: Slupsky
authors.forename: Thomas
authors.initials: T
authors.lastname: Marrie
authors.forename: Brian D
authors.initials: BD
authors.lastname: Sykes
authors.forename: Christopher
authors.initials: C
authors.lastname: Power
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D018792:Encephalitis, Viral / Q000473:pathology*; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D054892:Metagenome; D008875:Middle Aged; D011818:Rabies / Q000473:pathology*; D011820:Rabies virus / Q000472:pathogenicity*; D060888:Real-Time Polymerase Chain Reaction