title: JC virus VP1 loop-specific polymorphisms are associated with favorable prognosis for progressive multifocal leukoencephalopathy.
abstract: JC virus (JCV) is a human polyomavirus that causes progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease that mainly affects immunocompromised subjects. Since its discovery, PML has been considered a rapidly progressing fatal disease; however, amino acid substitutions in the capsid viral protein have recently been tentatively associated with changes in PML clinical course. In order to provide more insight to PML pathogenesis and identify potential prognostic markers, seven cerebrospinal fluid (CSF) samples and four brain autopsy samples were collected from patients afflicted with PML with different clinical courses (fast- and slow-progressing), and the JCV VP1 coding region was amplified, cloned, and sequenced. In addition, urine samples were collected and analyzed from nine patients with PML or other neurological diseases (ONDs) as a control group. Sequencing analysis of the genomic region encoding the VP1 outer loops revealed polymorphic residues restricted to four positions (74, 75, 117, and 128) in patients with slow PML progression, whereas no significant mutation was found in JCV isolated from urine. Collectively, these data show that JCV VP1 loop mutations are associated with a favorable prognosis for PML. It is therefore possible that slower progression of PML may be related to the emergence of a less virulent JCV strain with a lower replication rate.
authors.affiliation: Laboratory of Molecular Virology, Department of Biomedical Science and Technology, University of Milan, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Delbue
authors.forename: Emanuela
authors.initials: E
authors.lastname: Branchetti
authors.forename: Simone
authors.initials: S
authors.lastname: Bertolacci
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tavazzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Marchioni
authors.forename: Renato
authors.initials: R
authors.lastname: Maserati
authors.forename: Giulia
authors.initials: G
authors.lastname: Minnucci
authors.forename: Sara
authors.initials: S
authors.lastname: Tremolada
authors.forename: GianLuca
authors.initials: G
authors.lastname: Vago
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ferrante
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001921:Brain / Q000821:virology; D036022:Capsid Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D036022:Capsid Proteins; C062481:VP1 protein, polyomavirus