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Original Investigation
February 27, 2017

Distribution and Quantity of Sites of John Cunningham Virus Persistence in Immunologically Healthy PatientsCorrelation With John Cunningham Virus Antibody and Urine John Cunningham Virus DNA

Author Affiliations
  • 1Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 2Center for Oral Health Research, College of Dentistry, University of Kentucky College of Medicine, Lexington, Kentucky
  • 3Biogen, Cambridge, Massachusetts
  • 4Oncorus Inc, Cambridge, Massachusetts
  • 5Fortress Biotech, New York, New York
  • 6Department of Neurology, University of Oklahoma, Oklahoma City
  • 7Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland
  • 8Highlands Neurology, Prestonsburg, Kentucky
  • 9Department of Pathology, University of Kentucky College of Medicine, Lexington
JAMA Neurol. Published online February 27, 2017. doi:10.1001/jamaneurol.2016.5537
Key Points

Question  What is the distribution and quantity of John Cunningham virus (JCV) in the tissues of the immunocompetent host and how does it correlate with JCV antibody levels?

Findings  In this study of multiple tissues obtained from 12 immunocompetent persons, JCV predominated in renal-reproductive tissues but was observed in other organs, including brain, in low copy numbers. Tissue distribution and viral copy numbers, particularly urine JCV copy numbers, appeared to correlate with JCV antibody levels.

Meaning  High JCV antibody levels may be indicative of more widespread JCV distribution and replication.

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 on the tissue specimens and urine. Serum JCV antibody status was determined by enzyme-linked immunosorbent assay.

Main Outcomes and Measures  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 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.

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.

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