The antiviral drug ganciclovir does not inhibit microglial proliferation and activation.

Abstract

Ganciclovir is effective in the treatment of human infections with viruses of the Herpesviridae family. Beside antiviral properties, recently ganciclovir was described to inhibit microglial proliferation and disease severity of experimental autoimmune encephalomyelitis, an inflammatory model of multiple sclerosis. Microglial activation and proliferation are main characteristics of neuroinflammatory CNS diseases and inhibition of microglial functions might be beneficial in autoimmune diseases, or detrimental in infectious diseases. The objective of this study was to determine potential inhibitory effects of ganciclovir in three different murine animal models of CNS neuroinflammation in which microglia play an important role: Theiler´s murine encephalomyelitis, the cuprizone model of de- and remyelination, and the vesicular stomatitis virus encephalitis model. In addition, in vitro experiments with microglial cultures were performed to test the hypothesis that ganciclovir inhibits microglial proliferation. In all three animal models, neither microglial proliferation or recruitment nor disease activity was changed by ganciclovir. In vitro experiments confirmed that microglial proliferation was not affected by ganciclovir. In conclusion, our results show that the antiviral drug ganciclovir does not inhibit microglial activation and proliferation in the murine CNS.

• Authors: Thomas Skripuletz, Laura Salinas Tejedor, Chittappen K Prajeeth, Florian Hansmann, Chintan Chhatbar, Valeria Kucman, Ning Zhang, Barbara B Raddatz, Claudia N Detje, Kurt-Wolfram Sühs, Refik Pul, Viktoria Gudi, Ulrich Kalinke, Wolfgang Baumgärtner, Martin Stangel
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 14935 (Oct 08 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26447351 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Cuprizone
• Ganciclovir

Topics

• Animals
• Animals, Newborn
• Antiviral Agents (pharmacology)
• Brain (drug effects, pathology, virology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cuprizone
• Demyelinating Diseases (chemically induced, prevention & control)
• Disease Models, Animal
• Encephalomyelitis (prevention & control, virology)
• Ganciclovir (pharmacology)
• Host-Pathogen Interactions (drug effects)
• Humans
• Immunohistochemistry
• Macrophage Activation (drug effects, immunology)
• Mice, Inbred C57BL
• Microglia (drug effects, immunology, pathology)
• Theilovirus (physiology)
• Vesicular Stomatitis (prevention & control, virology)
• Vesiculovirus (physiology)