An siRNA against JC virus (JCV) agnoprotein inhibits JCV infection in JCV-producing cells inoculated in nude mice

Neuropathology : Official Journal of the Japanese Society of Neuropathology
Tomoko MatobaHirofumi Sawa

Abstract

JC virus (JCV) is the etiological agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). Because JCV has a very narrow host range, it has been difficult to develop an animal model of JCV infection; as a result, no effective therapy for PML has been established. In this study, we have tried to create an animal model that replaces an in vivo JCV infection. As a result, we have obtained a stable persistence of JCV-infected human cells in the mouse brain by inoculating the virus-infected cells into the nude mice brains. In this model, the JCV-infected cells were well preserved in the nude mouse brains for 2 weeks. We then treated JCV-injected brains with an siRNA against the JCV agnoprotein that is known to be an effective inhibitor of JCV infection in vitro. A highly purified type I collagen, atelocollagen, was used as a carrier for the siRNA. The siRNA inhibited the expression of JCV protein in inoculated JCV-infected cells in the mouse brain, compared to the medium containing only atelocollagen used as a placebo. Thus, the combination of siRNA and atelocollagen might be a candidate therapeutic agent for the treatment of JCV infection.

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Citations

Mar 20, 2010·PLoS Pathogens·Tadaki SuzukiHirofumi Sawa
May 27, 2014·Therapeutic Delivery·Ichiro Fujimoto, Yoshifumi Takei
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