Human polyomavirus JC replication and non-coding control region analysis in multiple sclerosis patients under natalizumab treatment.
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.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le Aldo Moro, 5, 00185, Rome, Italy. valeria.pietropaolo@uniroma1.it.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, USA. valeria.pietropaolo@uniroma1.it.
Valeria
V
Pietropaolo
Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci-Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.|Department of Neuroscience, Temple University School of Medicine, Philadelphia, USA.
Anna
A
Bellizzi
Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le Aldo Moro, 5, 00185, Rome, Italy.
Elena
E
Anzivino
Institut Cochin, Inserm U1016, Equipe Physiologie des cellules dendritiques, Paris, France.
Marco
M
Iannetta
Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le Aldo Moro, 5, 00185, Rome, Italy.
Maria Antonella
MA
Zingaropoli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le Aldo Moro, 5, 00185, Rome, Italy.
Donatella Maria
DM
Rodio
Department of Medico-Surgical Sciences and Biotechnologies, Section of Neurology, Sapienza University of Rome, Rome, Italy.
Manuela
M
Morreale
Istituto di Ricerca e Cura a Carattere Scientifico-Neuromed, Pozzilli, Isernia, Italy.
Simona
S
Pontecorvo
Multiple Sclerosis Center, Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
Ada
A
Francia
Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le Aldo Moro, 5, 00185, Rome, Italy.
Vincenzo
V
Vullo
Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci-Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.|San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, Rome, Italy.
Anna Teresa
AT
Palamara
Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le Aldo Moro, 5, 00185, Rome, Italy.
Maria Rosa
MR
Ciardi
D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis; D004279:DNA, Viral / Q000097:blood* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007577:JC Virus / Q000235:genetics*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000821:virology*; D000069442:Natalizumab / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load / Q000187:drug effects; D014766:Viremia; D014779:Virus Replication
D000914:Antibodies, Viral; D004279:DNA, Viral; D007155:Immunologic Factors; D000069442:Natalizumab
Multiple sclerosis; NCCR sequencing; Natalizumab; Polyomavirus JC; Real-time PCR; STRATIFY JCV®