Varied persistent life cycles of Borna disease virus in a human oligodendroglioma cell line

Madiha S. Ibrahim, Makiko Watanabe, J. Alejandro Palacios, Wataru Kamitani, Satoshi Komoto, Takeshi Kobayashi, Keizo Tomonaga, Kazuyoshi Ikuta

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7 Citations (Scopus)

Abstract

Borna disease virus (BDV) establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures. In an attempt to characterize the life cycle of BDV in persistently infected cultured cells, we developed 30 clones by single-cell cloning from a human oligodendroglioma (OL) cell line after infection with BDV. According to the percentage of cells expressing the BDV major proteins, p40 (nucleoprotein) and p24 (phosphoprotein), the clones were classified into two types: type I (>20%) and type II (<20%). mRNAs corresponding to both proteins were detected by in situ hybridization (ISH) in a percentage of cells consistent with that for the protein expression in the two types. Surprisingly, ISH for the detection of the genomic RNA, mainly in type II, revealed a significantly larger cell population harboring the genomic RNA than that with the protein as well as the mRNA expression. By recloning from type II primary cell clones, the same phenotype was confirmed in the secondary cell clones obtained: i.e., low percentage of protein-positive cells and higher percentage of cells harboring the genomic RNA. After nerve growth factor treatment, the two types of clones showed increases in the percentage of cells expressing BDV-specific proteins that reached 80% in type II clones, in addition to increased expression levels per cell. Such enhancement might have been mediated by the activation of the mitogen-activated protein kinase in the clones as revealed by the detection of activated ERK1/2. Thus, our findings show that BDV may have established a persistent infection at low levels of viral expression in OL cells with the possibility of a latent infection.

Original languageEnglish
Pages (from-to)3873-3880
Number of pages8
JournalJournal of Virology
Volume76
Issue number8
DOIs
Publication statusPublished - 2002

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Ibrahim, M. S., Watanabe, M., Palacios, J. A., Kamitani, W., Komoto, S., Kobayashi, T., Tomonaga, K., & Ikuta, K. (2002). Varied persistent life cycles of Borna disease virus in a human oligodendroglioma cell line. Journal of Virology, 76(8), 3873-3880. https://doi.org/10.1128/JVI.76.8.3873-3880.2002