title: Distribution and Quantity of Sites of John Cunningham Virus Persistence in Immunologically Healthy Patients: Correlation With John Cunningham Virus Antibody and Urine John Cunningham Virus DNA.
abstract: Although seroepidemiological studies indicate that greater than 50% of the population has been infected with John Cunningham virus (JCV), the sites of JCV persistence remain incompletely characterized.
  
  
  
  To determine sites of JCV persistence in immunologically healthy individuals.
  
  
  
  Tissue specimens from multiple sites including brain, renal, and nonrenal tissues were obtained at autopsy performed in the Department of Pathology at the University of Kentucky from 12 immunologically healthy patients between February 9, 2011, and November 27, 2012. Quantitative polymerase chain reaction was performed on the tissue specimens and urine. Serum JCV antibody status was determined by enzyme-linked immunosorbent assay.
  
  
  
  The detection and quantification of JCV from the tissues by quantitative polymerase chain reaction illuminated sites of viral persistence. These results were correlated with JCV antibody levels.
  
  
  
  Autopsies were performed on 12 individuals, 10 men and 2 women, ranging in age from 25 to 75 years (mean, 55.3 years). Seven of 12 individuals were JCV antibody seropositive based on absorbance units. Serostatus was associated with amounts of JCV DNA in urine and its tissue distribution. John Cunningham virus DNA was found in 75% of genitourinary tissue samples from donors (18 of 24) with high JCV antibody levels, 13.3% of donors with low levels i(4 of 30), and 0% of seronegative persons (0 of 32). In nongenitourinary tissues, JCV DNA was detected in 45.1% of tissue samples of donors (32 of 71) with high JCV, 2.2% of donors with low JCV serostatus (2 of 93), and 0% of seronegative persons (0 of 43). Genitourinary tissues had higher copy numbers than other sites. John Cunningham virus DNA was detected in urine of seronegative individuals in a research-grade assay.
  
  
  
  Persistent (latent or actively replicating) JCV infection mostly predominates in genitourinary tissues but distributes in other tissues at low copy number. The distribution and copy numbers of the virus appear to correlate with urinary JCV shedding and serostatus.
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Berger
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky College of Medicine, Lexington, Kentucky.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Miller
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky College of Medicine, Lexington, Kentucky.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Danaher
authors.affiliation: Biogen, Cambridge, Massachusetts.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Doyle
authors.affiliation: Oncorus Inc, Cambridge, Massachusetts.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Simon
authors.affiliation: Biogen, Cambridge, Massachusetts.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Norton
authors.affiliation: Fortress Biotech, New York, New York.
authors.forename: Leonid
authors.initials: L
authors.lastname: Gorelik
authors.affiliation: Biogen, Cambridge, Massachusetts.
authors.forename: Ellen
authors.initials: E
authors.lastname: Cahir-McFarland
authors.affiliation: Department of Neurology, University of Oklahoma, Oklahoma City.
authors.forename: Divya
authors.initials: D
authors.lastname: Singhal
authors.affiliation: Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland.
authors.forename: Nawaz
authors.initials: N
authors.lastname: Hack
authors.affiliation: Highlands Neurology, Prestonsburg, Kentucky.
authors.forename: Joseph Ryan
authors.initials: JR
authors.lastname: Owens
authors.affiliation: Department of Pathology, University of Kentucky College of Medicine, Lexington.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.affiliation: Department of Pathology, University of Kentucky College of Medicine, Lexington.
authors.forename: Janna H
authors.initials: JH
authors.lastname: Neltner
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D001344:Autopsy; D004279:DNA, Viral / Q000652:urine*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007577:JC Virus / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000276:immunology; D016036:Seroepidemiologic Studies; D014018:Tissue Distribution; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral