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An siRNA against JC virus (JCV) agnoprotein inhibits JCV infection in JCV‐producing cells inoculated in nude mice
Author(s) -
Matoba Tomoko,
Orba Yasuko,
Suzuki Tadaki,
Makino Yoshinori,
Shichinohe Hideo,
Kuroda Satoshi,
Ochiya Takahiro,
Itoh Hiroshi,
Tanaka Shinya,
Nagashima Kazuo,
Sawa Hirofumi
Publication year - 2008
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2007.00878.x
Subject(s) - jc virus , virology , progressive multifocal leukoencephalopathy , demyelinating disease , in vivo , in vitro , virus , biology , cancer research , immunology , multiple sclerosis , biochemistry , microbiology and biotechnology
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.