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Journal of Virology, November 2002, p. 11397-11404, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11397-11404.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effective Postexposure Treatment of Retrovirus-Induced Disease with Immunostimulatory DNA Containing CpG Motifs

Anke R. M. Olbrich,1 Simone Schimmer,1 Klaus Heeg,2 Koen Schepers,3 Ton N. M. Schumacher,3 and Ulf Dittmer1*

Institut für Virologie der Universität Würzburg, 97078 Würzburg,1 Institut für Medizinische Mikrobiologie und Hygiene, Universität Marburg, Marburg, Germany,2 Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands3

Received 7 May 2002/ Accepted 19 August 2002

Therapeutic strategies for the treatment of acute retroviral infections have relied mainly on antiviral drugs. In this study we used the Friend virus model system to demonstrate that enhancement of the immune system can also have dramatic therapeutic effects. Since resistance to Friend virus-induced leukemia in mice is associated with T helper cell type 1 (Th1) immune responses, we enhanced these responses in susceptible mice by treatment with synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN). Treatments begun at 4 days postinfection increased recovery from 6% in the control group to 74% in the CpG-treated group. CpG-mediated recovery was associated with a significant reduction of viral loads in the blood and spleens of treated mice compared to those of control animals. The treatment promoted Th1-type cytokine production by splenocytes of Friend virus-infected mice and augmented Friend virus-specific cytotoxic T-cell responses, but no influence on the virus-specific neutralizing antibody response was observed. Friend virus-specific CD8+ T cells were critical for effective treatment with CpG-ODN, since in vivo depletion of these cells from treated mice prevented their recovery. Our results demonstrate that CpG-ODN therapy can significantly enhance virus-specific cellular immune responses and prevent retrovirus-induced disease. These findings may have implications for antiviral therapy in general.

* Corresponding author. Mailing address: Institut für Virologie, Universität Essen, Hufelandstr. 55, 45122 Essen, Germany. Phone: 49-201-723-3561. Fax: 49-201-723-5929. E-mail: ulf.dittmer{at}uni-essen.de.

Journal of Virology, November 2002, p. 11397-11404, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11397-11404.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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