HIV-associated progressive multifocal leukoencephalopathy: Longitudinal study of JC virus non-coding control region rearrangements and host immunity

Marco Iannetta, Anna Bellizzi, Sara Lo Menzo, Elena Anzivino, Alessandra D'Abramo, Alessandra Oliva, Claudia D'Agostino, Gabriella D'Ettorre, Valeria Pietropaolo, Vincenzo Vullo, Maria Rosa Ciardi

Research output: Contribution to journalArticlepeer-review

Abstract

John Cunningham virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy (PML), contains a hyper-variable non-coding control region usually detected in urine of healthy individuals as archetype form and in the brain and cerebrospinal fluid (CSF) of PML patients as rearranged form. We report a case of HIV-related PML with clinical, immunological and virological data longitudinally collected. On admission (t0), after 8-week treatment with a rescue highly active antiretroviral therapy (HAART), the patient showed a CSF-JCV load of 16,732 gEq/ml, undetectable HIV-RNA and an increase of CD4+ cell count. Brain magnetic resonance imaging (MRI) showed PML-compatible lesions without contrast enhancement. We considered PML-immune reconstitution inflammatory syndrome as plausible because of the sudden onset of neurological symptoms after the effective HAART. An experimental JCV treatment with mefloquine and mirtazapine was added to steroid boli. Two weeks later (t1), motor function worsened and MRI showed expanded lesions with cytotoxic oedema. CSF JCV-DNA increased (26,263 gEq/ml) and JCV viremia was detected. After 4 weeks (t2), JCV was detected only in CSF (37,719 gEq/ml), and 8 weeks after admission (t3), JC viral load decreased in CSF and JCV viremia reappeared. The patient showed high level of immune activation both in peripheral blood and CSF. He died 4 weeks later. Considering disease progression, combined therapy failure and immune hyper-activation, we finally classified the case as classical PML. The archetype variant found in CSF at t0/t3 and a rearranged sequence detected at t1/t2 suggest that PML can develop from an archetype virus and that the appearance of rearranged genotypes contribute to faster disease progression.

Original languageEnglish
Pages (from-to)274-279
Number of pages6
JournalJournal of NeuroVirology
Volume19
Issue number3
DOIs
Publication statusPublished - Jun 2013

Keywords

  • HIV
  • Immune activation
  • IRIS
  • JCV-NCCR
  • PML

ASJC Scopus subject areas

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

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