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Journal of Virology, December 2006, p. 12079-12085, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01456-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

NFAT4 Is Required for JC Virus Infection of Glial Cells{triangledown}

Kate Manley,1 Bethany A. O'Hara,2 Gretchen V. Gee,2 Carl P. Simkevich,2 John M. Sedivy,2 and Walter J. Atwood2*

Graduate Program in Molecular Biology, Cell Biology and Biochemistry,1 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 029122

Received 10 July 2006/ Accepted 27 September 2006

The human polyomavirus JC virus (JCV) infects 70% of the population worldwide. In immunosuppressed patients, JCV infection can lead to progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS). The majority of PML cases occur in the setting of human immunodeficiency virus (HIV) infection, and it has been suggested that the link between HIV and the development of PML is in part related to the production of numerous cytokines in the CNS during HIV infection. To examine the link between the expression of inflammatory cytokines and JCV infection, we tested an anti-inflammatory compound, cyclosporine A (CsA), for its ability to block JCV infection of glial cells. We found that CsA inhibited JCV infection by preventing the activation of the transcription factor nuclear factor of activated T cells 4 (NFAT4). Luciferase reporter assays and chromatin immunoprecipitation assays revealed that NFAT4 directly bound the JCV promoter during infection and was important for the activation of both early and late transcription. In addition, the expression of the JCV early viral gene products increased NFAT activity to further aid viral transcription. The necessity of NFAT for JCV infection suggests that calcium signaling and the activation of NFAT in glial cells are required for JCV infection of the CNS.

* Corresponding author. Mailing address: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912. Phone: (401) 863-3116. Fax: (401) 863-9653. E-mail: Walter_Atwood{at}Brown.edu.

{triangledown} Published ahead of print on 11 October 2006.

Journal of Virology, December 2006, p. 12079-12085, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01456-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Nived, O, Bengtsson, A., Jonsen, A, Sturfelt, G (2008). Progressive multifocal leukoencephalopathy - the importance of early diagnosis illustrated in four cases. Lupus 17: 1036-1041 [Abstract]  


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