An siRNA against JC virus (JCV) agnoprotein inhibits JCV infection in JCV-producing cells inoculated in nude mice.
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.
Matoba
Tomoko
T
Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Orba
Yasuko
Y
Suzuki
Tadaki
T
Makino
Yoshinori
Y
Shichinohe
Hideo
H
Kuroda
Satoshi
S
Ochiya
Takahiro
T
Itoh
Hiroshi
H
Tanaka
Shinya
S
Nagashima
Kazuo
K
Sawa
Hirofumi
H
D000818:Animals; D003094:Collagen / Q000008:administration & dosage; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics; D007968:Leukoencephalopathy, Progressive Multifocal / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D027601:Polyomavirus Infections / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014412:Tumor Virus Infections / Q000628:therapy*; D054334:Viral Regulatory and Accessory Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D000086082:Viroporin Proteins
D003094:Collagen; D034741:RNA, Small Interfering; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins; C059821:atelocollagen