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

Joseph R. Berger, Craig S. Miller, Robert J. Danaher, Kathryn Doyle, Kenneth J. Simon, Elizabeth Norton, Leonid Gorelik, Ellen Cahir-McFarland, Divya Singhal, Nawaz Hack, Joseph Ryan Owens, Peter T. Nelson, Janna H. Neltner

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

IMPORTANCE: 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. OBJECTIVE: To determine sites of JCV persistence in immunologically healthy individuals. DESIGN, SETTING, AND PARTICIPANTS: 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 onthe tissue specimens and urine. Serum JCV antibody status was determined by enzyme-linked immunosorbent assay. MAINOUTCOMES ANDMEASURES: 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. RESULTS: Autopsies were performedon 12 individuals, 10 men and 2 women, rangingin 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. CONCLUSIONS AND RELEVANCE: 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.

Original languageEnglish
Pages (from-to)437-444
Number of pages8
JournalJAMA Neurology
Volume74
Issue number4
DOIs
StatePublished - Apr 1 2017

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Copyright 2017 American Medical Association. All rights reserved.

ASJC Scopus subject areas

  • Clinical Neurology

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