Human polyomavirus JC replication and non-coding control region analysis in multiple sclerosis patients under natalizumab treatment

Valeria Pietropaolo, Anna Bellizzi, Elena Anzivino, Marco Iannetta, Maria Antonella Zingaropoli, Donatella Maria Rodio, Manuela Morreale, Simona Pontecorvo, Ada Francia, Vincenzo Vullo, Anna Teresa Palamara, Maria Rosa Ciardi

Research output: Contribution to journalArticlepeer-review

Abstract

In the last years, the treatment of multiple sclerosis (MS) patients with natalizumab has been associated with the occurrence of progressive multifocal leukoencephalopathy (PML) caused by human polyomavirus JC (JCV). Here, we have shown a significant correlation between patients with JC viruria and positive JC-specific antibody response and patients without JCV-specific antibodies after 1 year of natalizumab (p = 0.0006). Furthermore, JCV-specific quantitative PCR on urine and plasma samples, collected at the enrollment (t0) and every 4 months (t1, t2, t3) in the first year and at two time points (t4 and t5) in the second year of natalizumab treatment, indicated the prevalence of JC viremia rather than JC viruria only in the second year of treatment (p = 0.04). Moreover, the analysis of JCV non-coding control region (NCCR) sequences in peripheral blood mononuclear cells of patients with JC-specific antibodies after 12 natalizumab infusions (t3) revealed the presence of rearranged sequences, whereas the prevalence of genotypes 1A, 1B, and 4 was detected in these patients by VP1 sequence analysis. In summary, JC viruria evaluation seems to be useful to identify early those patients who do not already develop a humoral immune response against JCV. It may also be interesting to study the JCV NCCR rearrangements since they could give us new insights on the onset of neuro-invasive viral variants.

Original languageEnglish
Pages (from-to)653-665
Number of pages13
JournalJournal of NeuroVirology
Volume21
Issue number6
DOIs
Publication statusPublished - May 1 2015

Keywords

  • Multiple sclerosis
  • Natalizumab
  • NCCR sequencing
  • Polyomavirus JC
  • Real-time PCR
  • STRATIFY JCV

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Neurology

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