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

被引：26

作者：

Matoba, Tomoko ^{[2
]}

Orba, Yasuko ^{[1
,2
]}

Suzuki, Tadaki ^{[1
]}

Makino, Yoshinori ^{[1
,4
]}

Shichinohe, Hideo ^{[3
]}

Kuroda, Satoshi ^{[3
]}

Ochiya, Takahiro ^{[6
]}

Itoh, Hiroshi ^{[7
]}

Tanaka, Shinya ^{[2
]}

Nagashima, Kazuo ^{[2
,5
]}

Sawa, Hirofumi ^{[1
,4
]}

机构：

[1] Hokkaido Univ, Res Ctr Zoonosis Control, Kita Ku, Dept Mol Pathol, Sapporo, Hokkaido 00010020, Japan

[2] Hokkaido Univ, Grad Sch Med, Lab Mol & Cellular Pathol, Sapporo, Hokkaido 060, Japan

[3] Hokkaido Univ, Grad Sch Med, Dept Neurosurg, Sapporo, Hokkaido 060, Japan

[4] Hokkaido Univ, Century COE Program Zoonosis Control 21, Sapporo, Hokkaido 060, Japan

[5] Sapporo Higashi Tokushukai Hosp, Dept Pathol, Sapporo, Hokkaido, Japan

[6] Natl Canc Ctr, Sect Studies Metastasis, Tokyo, Japan

[7] Koken Co Ltd, Tokyo, Japan

来源：

NEUROPATHOLOGY | 2008年 / 28卷 / 03期

关键词：

atelocollagen; JC virus agnoprotein; siRNA;

D O I：

10.1111/j.1440-1789.2007.00878.x

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：286 / 294

页数：9

共 36 条

[1] RNAi puts a lid on virus replication [J].

Andino, R .

NATURE BIOTECHNOLOGY, 2003, 21 (06) :629-630

[2] Meningoencephalitis and demyelination are pathologic manifestations of primary polyomavirus infection in immunosuppressed rhesus monkeys [J].

Axthelm, MK ;

Koralnik, IJ ;

Dang, X ;

Wüthrich, C ;

Rohne, D ;

Stillman, IE ;

Letvin, NL .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2004, 63 (07) :750-758

[3] Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy [J].

Berenguer, J ;

Miralles, P ;

Arrizabalaga, J ;

Ribera, E ;

Dronda, F ;

Baraia-Etxaburu, J ;

Domingo, P ;

Márquez, M ;

Rodriguez-Arrondo, FJ ;

Laguna, F ;

Rubio, R ;

Rodrigo, JL ;

Mallolas, J ;

de Miguel, V .

CLINICAL INFECTIOUS DISEASES, 2003, 36 (08) :1047-1052

[4] Role for a bidentate ribonuclease in the initiation step of RNA interference [J].

Bernstein, E ;

Caudy, AA ;

Hammond, SM ;

Hannon, GJ .

NATURE, 2001, 409 (6818) :363-366

[5] Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems [J].

Caplen, NJ ;

Parrish, S ;

Imani, F ;

Fire, A ;

Morgan, RA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9742-9747

[6] The effect of highly active antiretroviral therapy-induced immune reconstitution on development and outcome of progressive multifocal leukoencephalopathy: Study of 43 cases with review of the literature [J].

Cinque, P ;

Bossolasco, S ;

Brambilla, AM ;

Boschini, A ;

Mussini, C ;

Pierotti, C ;

Campi, A ;

Casari, S ;

Bertelli, D ;

Mena, M ;

Lazzarini, A .

JOURNAL OF NEUROVIROLOGY, 2003, 9 (Suppl 1) :73-80

[7] Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].

Elbashir, SM ;

Harborth, J ;

Lendeckel, W ;

Yalcin, A ;

Weber, K ;

Tuschl, T .

NATURE, 2001, 411 (6836) :494-498

[8] HUMAN POLYOMAVIRUS JC-VIRUS GENOME [J].

FRISQUE, RJ ;

BREAM, GL ;

CANNELLA, MT .

JOURNAL OF VIROLOGY, 1984, 51 (02) :458-469

[9] RNA interference of influenza virus production by directly targeting rnRNA for degradation and indirectly inhibiting all viral RNA transcription [J].

Ge, Q ;

McManus, MT ;

Nguyen, T ;

Shen, CH ;

Sharp, PA ;

Eisen, HN ;

Chen, JZ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2718-2723

[10] Short interfering RNA confers intracellular antiviral immunity in human cells [J].

Gitlin, L ;

Karelsky, S ;

Andino, R .

NATURE, 2002, 418 (6896) :430-434

← 1 2 3 4 →