New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid protein (VP1) possibly associated with progressive multifocal leukoencephalopathy.
JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in patients with decreased immune competence. To elucidate genetic changes in JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones originating from the brains of three PML cases were established and sequenced. Although unique rearranged control regions occurred in all clones, a low level of nucleotide variation was also found in the coding region. In each case, a parental coding sequence was identified, from which variant coding sequences with nucleotide substitutions would have been generated. A comparison between the parental and variant coding sequences demonstrated that all 12 detected nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of these changes were located in the surface loops of the major capsid protein (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from the brain or cerebrospinal fluid of PML patients) were compared with their genotypic prototypes, generated as consensus sequences of representative archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino acid changes in the surface loops. In contrast, VP1 proteins from isolates from the urine of immunocompetent and immunosuppressed patients rarely underwent mutations in the VP1 loops. The present findings suggest that PML-type JCPyV frequently undergoes amino acid substitutions in the VP1 loops. These polymorphisms should serve as a new marker for the identification of JCPyV isolates associated with PML. The biological significance of these mutations, however, remains unclear.
Zheng
Huai-Ying
HY
Japanese Foundation for AIDS Prevention, Tokyo 105-0001, Japan.|Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Takasaka
Tomokazu
T
Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Noda
Kazuyuki
K
Department of Neurology, Juntendo University School of Medicine, Tokyo 113-0033, Japan.
Kanazawa
Akira
A
Department of Neurology, Juntendo University School of Medicine, Tokyo 113-0033, Japan.
Mori
Hideo
H
Department of Neurology, Juntendo University School of Medicine, Tokyo 113-0033, Japan.
Kabuki
Tomoyuki
T
Division of Infectious Diseases, Immunology and Allergy, Saitama Children's Medical Center, Iwatsuki 339-8551, Japan.
Joh
Kohsuke
K
Division of Infectious Diseases, Immunology and Allergy, Saitama Children's Medical Center, Iwatsuki 339-8551, Japan.
Oh-Ishi
Tsutomu
T
Division of Infectious Diseases, Immunology and Allergy, Saitama Children's Medical Center, Iwatsuki 339-8551, Japan.
Ikegaya
Hiroshi
H
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Nagashima
Kazuo
K
Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, CREST, Japan.
Hall
William W
WW
Department of Medical Microbiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Kitamura
Tadaichi
T
Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yogo
Yoshiaki
Y
Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
D000328:Adult; D019943:Amino Acid Substitution; D001921:Brain / Q000821:virology; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics*; D002555:Cerebrospinal Fluid / Q000821:virology; D005260:Female; D006801:Humans; D007577:JC Virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000503:physiopathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014556:Urine / Q000821:virology
D036022:Capsid Proteins; C062481:VP1 protein, polyomavirus