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New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid protein (VP1) possibly associated with progressive multifocal leukoencephalopathy

¹ Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
² Japanese Foundation for AIDS Prevention, Tokyo 105-0001, Japan
³ Department of Neurology, Juntendo University School of Medicine, Tokyo 113-0033, Japan
⁴ Division of Infectious Diseases, Immunology and Allergy, Saitama Children's Medical Center, Iwatsuki 339-8551, Japan
⁵ Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
⁶ Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, CREST, Japan
⁷ Department of Medical Microbiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland

Correspondence
Yoshiaki Yogo
yogo-tky{at}umin.ac.jp

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.

The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this paper are AB183534–AB183544 and AB190446–AB190453 (see Table 1).