title: Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive multifocal leukoencephalopathy.
abstract: Recently, we found that JC polyomavirus (JCPyV) associated with progressive multifocal leukoencephalopathy (PML) frequently undergoes amino acid substitutions (designated VP1 loop mutations) in the outer loops of the major capsid protein, VP1. To further characterize the mutations, we analyzed the VP1 region of the JCPyV genome in brain-tissue or cerebrospinal fluid samples from 20 PML patients. VP1 loop mutations occurred far more frequently than silent mutations. Polymorphic residues were essentially restricted to three positions (55, 60, and 66) within the BC loop, one (123) within the DE loop, and three (265, 267, and 269) within the HI loop. The mutations at most polymorphic residues showed a trend toward a change to specific amino acids. Finally, we presented evidence that the VP1 loop mutations were associated with the progression of PML. These findings should form the basis for elucidating the biological significance of the VP1 loop mutations.
authors.affiliation: Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Huai-Ying
authors.initials: HY
authors.lastname: Zheng
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegaya
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Takasaka
authors.forename: Takae
authors.initials: T
authors.lastname: Matsushima-Ohno
authors.forename: Masaki
authors.initials: M
authors.lastname: Sakurai
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Kishida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagashima
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yogo
mesh_terms: D001344:Autopsy; D001483:Base Sequence; D001921:Brain / Q000473:pathology / Q000821:virology; D036022:Capsid Proteins / Q000737:chemistry / Q000302:isolation & purification; D017931:DNA Primers; D004279:DNA, Viral / Q000134:cerebrospinal fluid / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D036022:Capsid Proteins; D017931:DNA Primers; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus