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Sequential changes in the non-coding control region sequences of JC polyomaviruses from the cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy

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Abstract

Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus (JCV) infection in the brain. JCV isolates from PML patients have variable mutations in the non-coding control region (NCCR) of the genome. This study was conducted to examine sequential changes in NCCR patterns of JCV isolates obtained from the cerebrospinal fluid (CSF) of PML patients. CSF specimens were collected from PML patients at different time points, the NCCR sequences were determined, and their compositions were assessed by computer-based analysis. In patients showing a marked increase in JCV load, the most frequent NCCR sequences in the follow-up specimens were different from those in the initial samples. In contrast, the dominant NCCRs in the CSF remained unaltered during the follow-up of individuals in whom the viral load decreased after therapeutic intervention. These data demonstrate that the majority of JCV variants emerge with the progression of PML and that these changes are suppressed when the viral load is decreased.

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Acknowledgements

The authors are indebted to Dr. Souichi Nukuzuma, Kobe Institute of Health, and Dr. Akira Taniguchi, Mie University, for their valuable advice. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (22790446) as well as from the Research Committee of Prion Disease and Slow Virus Infection (H22-Nanchi-Ippan-013), the Research for Intractable Infectious Diseases in Organ Transplant Recipients (H21-Shinko-Ippan-009), and the Research on HIV/AIDS (H24-AIDS-Wakate-002) from the Ministry of Health, Labour and Welfare of Japan.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Virology 1, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan

    Kazuo Nakamichi, Ichiro Kurane, Chang-Kweng Lim & Masayuki Saijo

  2. Division of Neurology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, 113-8677, Japan

    Shuji Kishida & Kozue Tanaka

  3. Department of Infectious Diseases, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, 113-8677, Japan

    Akihiko Suganuma

  4. Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan

    Yasuteru Sano, Hironori Sano & Takashi Kanda

  5. Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Norihisa Maeda & Jun-ichi Kira

  6. Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan

    Ai Itoh, Natsuko Kato & Hidekazu Tomimoto

  7. Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan

    Hidehiro Mizusawa

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  1. Kazuo Nakamichi
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Nakamichi, K., Kishida, S., Tanaka, K. et al. Sequential changes in the non-coding control region sequences of JC polyomaviruses from the cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy. Arch Virol 158, 639–650 (2013). https://doi.org/10.1007/s00705-012-1532-3

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