Sequencing and analysis of JC virus DNA from natalizumab-treated PML patients

Carl E. Reid, Huo Li, Gargi Sur, Paul Carmillo, Steven Bushnell, Rich Tizard, Michele McAuliffe, Christopher Tonkin, Kenneth Simon, Susan Goelz, Paola Cinque, Leonid Gorelik, John P. Carulli

Research output: Contribution to journalArticlepeer-review


Background. Progressive multifocal leukoencephalopathy (PML) in natalizumab-treated MS patients is linked to JC virus (JCV) infection. JCV sequence variation and rearrangements influence viral pathogenicity and tropism. To better understand PML development, we analyzed viral DNA sequences in blood, CSF and/or urine of natalizumab-treated PML patients. Methods. Using biofluid samples from 17 natalizumab-treated PML patients, we sequenced multiple isolates of the JCV noncoding control region (NCCR), VP1 capsid coding region, and the entire 5 kb viral genome. Results. Analysis of JCV from multiple biofluids revealed that individuals were infected with a single genotype. Across our patient cohort, multiple PML-associated NCCR rearrangements and VP1 mutations were present in CSF and blood, but absent from urine-derived virus. NCCR rearrangements occurred in CSF of 100% of our cohort. VP1 mutations were observed in blood or CSF in 81% of patients. Sequencing of complete JCV genomes demonstrated that NCCR rearrangements could occur without VP1 mutations, but VP1 mutations were not observed without NCCR rearrangement. Conclusions. These data confirm that JCV in natalizumab-PML patients is similar to that observed in other PML patient groups, multiple genotypes are associated with PML, individual patients appear to be infected with a single genotype, and PML-associated mutations arise in patients during PML development.

Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalJournal of Infectious Diseases
Issue number2
Publication statusPublished - Jul 15 2011

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy


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