title: Molecular and bioinformatic evidence of hepatitis C virus evolution in brain.
abstract: BACKGROUND
  Neurocognitive deficits in patients with hepatitis C virus (HCV) infection prompted a search for HCV in brain.
  
  
  RESULTS
  HCV was present in the brains of 7 (54%) of 13 patients with viremia, as determined by 5' UTR and E1 (envelope 1) gene analysis. Brain HCV RNA consensus sequences differed from those in plasma and liver in 4 (57%) of 7 patients. The quality of HCV RNA from postmortem brain and liver was assessed and demonstrated to be suitable for sequence analysis. Quasispecies analysis revealed that several mutations present in clones from >1 brain region were absent in clones from liver and plasma. Brain-specific mutations defined several families of related sequences. The patterns of brain-specific mutations in these families were consistent with the evolution of HCV RNA from a common ancestor. Single-nucleotide-polymorphism analysis confirmed that a prominent brain-specific mutation constituted approximately 10% of HCV RNA in cerebellum and medulla but that this mutation was undetectable in the liver and plasma of the same patient.
  
  
  CONCLUSIONS
  This study introduces novel methods for assessing RNA from postmortem samples. It increases the reported cases of HCV in the brain, provides the first E1 sequences from the brain, and contributes to the growing evidence that HCV replicates and evolves within the brain.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Fishman
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: Murray
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Eng
authors.forename: José L
authors.initials: JL
authors.lastname: Walewski
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Branch
mesh_terms: D000595:Amino Acid Sequence; D001344:Autopsy; D001921:Brain / Q000821:virology*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000821:virology*; D006801:Humans; D008099:Liver / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012335:RNA, Ribosomal / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics*; D014779:Virus Replication
chemical_list: D012335:RNA, Ribosomal; D012367:RNA, Viral