Transcription of a human neurotropic virus promoter in glial cells: Effect of YB-1 on expression of the JC virus late gene

Douglas Kerr, Chun Fan Chang, Nancie Chen, Gary Gallia, Ganesh Raj, Benjamin Schwartz, Kamel Khalili

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Abstract

We have isolated a partial recombinant cDNA clone from a HeLa expression library which encodes a protein capable of binding to the central region of the human neurotropic JC virus (JCV) enhancer/promoter, termed the B region. Sequence analysis revealed a complete homology of the partial cDNA clone to the N-terminal region of a previously described DNA-binding protein, termed YB-1. Band shift analyses have indicated that the bacterially produced YB-1 interacts specifically with the double-stranded B oligonucleotide as well as the corresponding single-stranded DNA fragment representing the early promoter sequence. Further analysis indicated that the YB-1 protein binds specifically to the C/T-rich sequence of the B domain, which is located in close proximity to the TATA box within the virus enhancer/promoter. Results from cotransfection experiments demonstrated that the full-length (YB-1) but not the partial cDNA enhances expression of the JCV late (JCV(L)) promoter in glial cells. Cointroduction into glial cells of a recombinant expressing the YB-1 and JCV(L) deletion mutants indicated that removal of the C/T-rich sequence of the B domain reduces the level of activation of the virus promoter by YB-1. Further cotransfection experiments revealed that the virus transactivating protein T antigen appears to diminish the ability of YB-1 to activate JCV(L) gene expression. RNA studies indicated that YB-1 is expressed in several cell types and tissues. Examination of YB-1 RNA from mouse brain at various stages of development revealed high levels of YB-1 RNA at early stages of development and lower levels at all subsequent developmental stages.

Original languageEnglish (US)
Pages (from-to)7637-7643
Number of pages7
JournalJournal of Virology
Volume68
Issue number11
Publication statusPublished - Nov 1994

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ASJC Scopus subject areas

  • Immunology

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Kerr, D., Chang, C. F., Chen, N., Gallia, G., Raj, G., Schwartz, B., & Khalili, K. (1994). Transcription of a human neurotropic virus promoter in glial cells: Effect of YB-1 on expression of the JC virus late gene. Journal of Virology, 68(11), 7637-7643.