Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive multifocal leukoencephalopathy.
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.
Zheng
Huai-Ying
HY
Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Ikegaya
Hiroshi
H
Takasaka
Tomokazu
T
Matsushima-Ohno
Takae
T
Sakurai
Masaki
M
Kanazawa
Ichiro
I
Kishida
Shuji
S
Nagashima
Kazuo
K
Kitamura
Tadaichi
T
Yogo
Yoshiaki
Y
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
D036022:Capsid Proteins; D017931:DNA Primers; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus