Inhibition of measles virus and subacute sclerosing panencephalitis virus by RNA interference

Otaki, Momoko; Sada, Kiyonao; Kadoya, Hiroyasu; Nagano-Fujii, Motoko; Hotta, Hak

doi:10.1016/j.antiviral.2006.01.009

Cited by 22 publications

(24 citation statements)

References 45 publications

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“…In this context, the DNA polymerase or IVa2 genes could be of interest, as their knockdown RNAi proved more effective than that of E1A (37,38). Similarly, aptazyme regulation of the measles virus P or L polymerase genes or of the nucleocapsid N gene may facilitate conditional virus replication, as indicated by RNAi studies (39,40). Finally, the pace of shutting down established virus infections can most certainly be accelerated considerably by combined control of several viral genes blocking viral infections simultaneously at different stages of the virus replication cycle.…”

Section: Discussionmentioning

confidence: 99%

Artificial riboswitches for gene expression and replication control of DNA and RNA viruses

Ketzer

Kaufmann

Engelhardt

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

100

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Aptazymes are small, ligand-dependent self-cleaving ribozymes that function independently of transcription factors and can be customized for induction by various small molecules. Here, we introduce these artificial riboswitches for regulation of DNA and RNA viruses. We hypothesize that they represent universally applicable tools for studying viral gene functions and for applications as a safety switch for oncolytic and live vaccine viruses. Our study shows that the insertion of artificial aptazymes into the adenoviral immediate early gene E1A enables small-molecule-triggered, dosedependent inhibition of gene expression. Aptazyme-mediated shutdown of E1A expression translates into inhibition of adenoviral genome replication, infectious particle production, and cytotoxicity/ oncolysis. These results provide proof of concept for the aptazyme approach for effective control of biological outcomes in eukaryotic systems, specifically in virus infections. Importantly, we also demonstrate aptazyme-dependent regulation of measles virus fusion protein expression, translating into potent reduction of progeny infectivity and virus spread. This not only establishes functionality of aptazymes in fully cytoplasmic genetic systems, but also implicates general feasibility of this strategy for application in viruses with either DNA or RNA genomes. Our study implies that gene regulation by artificial riboswitches may be an appealing alternative to Tet-and other protein-dependent gene regulation systems, based on their small size, RNA-intrinsic mode of action, and flexibility of the inducing molecule. Future applications range from gene analysis in basic research to medicine, for example as a safety switch for new generations of efficiency-enhanced oncolytic viruses.

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Section: Discussionmentioning

confidence: 99%

Artificial riboswitches for gene expression and replication control of DNA and RNA viruses

Ketzer

Kaufmann

Engelhardt

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

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“…We previously reported that siRNAs targeted against the L mRNA of the MV genome (MV-L2, -L4 and -L5) efficiently inhibited replication of both MV and SSPE virus (26). We generated three strains of rAd-siRNA each expressing either one of the three different siR- NAs.…”

Section: Generation Of Rad-sirnamentioning

confidence: 99%

“…Assessment of inhibitory effects of rAd-siRNA on SSPE-Kobe-1 virus replication was performed as reported previously with some modifications (26). In brief, 6 hr after cell seeding, SSPE virus-infected or uninfected Vero/SLAM cells were inoculated with rAdsiRNA at indicated m.o.i.…”

Section: Cells and Mv/sspe Virus Strainsmentioning

confidence: 99%

“…rAd-siRNA was generated by AdMax TM Adenovirus Vector Creation system (Microbix Biosystems, Inc., Toronto, Ontario, Canada), according to the manufacturer's protocol. In brief, expression cassette of siRNA, which was designed to target the L mRNA of the MV genome, was derived from the pcPURϩU6i plasmid-based MV siRNA (26) and cloned into the BamHI and BglII multi-cloning site of pDC312 shuttle plasmid (Microbix Biosystems, Inc.). The shuttle plasmid construct was cotransfected with pBHGlox∆E1,3 Cre harboring the entire adenoviral genome (serotype 5) into 293T cells by using FuGene 6 reagent (Roche).…”

Section: Cells and Mv/sspe Virus Strainsmentioning

confidence: 99%

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Generation of Recombinant Adenovirus Expressing siRNA against the L mRNA of Measles Virus and Subacute Sclerosing Panencephalitis Virus

Otaki

Jiang

Sasayama

et al. 2007

Microbiology and Immunology

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Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by prolonged persistent infection of the central nervous system with a measles virus (MV) mutant called SSPE virus. At present, there is no effective treatment to completely cure SSPE and development of a new therapeutic measure(s) against this fatal slow virus infection is needed. We previously reported that replication of MV and SSPE virus was effectively inhibited by small interfering RNA (siRNA), either chemically synthetic or plasmid‐driven ones, that were targeted against different sequences of the mRNA for the L protein of MV. In this study, we have generated recombinant adenovirus expressing the siRNAs (rAd‐siRNA‐MV‐L2, ‐L4 and ‐L5) and demonstrated that these rAd‐siRNAs efficiently inhibited replication of MV and SSPE virus in a dose‐dependent manner. Due to their high capacity for gene delivery to nerve cells and the potential to inhibit SSPE virus replication, the rAd‐siRNAs could be a good candidate for a novel therapeutic measure against SSPE.

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“…Small interfering RNAs (siRNAs) have also been described to be active against MV (20,29,32), including an MV isolate from an SSPE patient (SSPE-Kobe-1) (28). In the latter approach, the authors generated recombi-nant adenoviruses (rAdV) expressing siRNA against MV L mRNA and assessed them in freshly infected Vero/SLAM cells.…”

mentioning

confidence: 99%

Clearance of Measles Virus from Persistently Infected Cells by Short Hairpin RNA

Zinke

Kendl

Singethan

et al. 2009

J Virol

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Subacute sclerosing panencephalitis (SSPE) is a demyelinating central nervous system disease caused by a persistent measles virus (MV) infection of neurons and glial cells.There is still no specific therapy available, and in spite of an intact innate and adaptive immune response, SSPE leads inevitably to death. In order to select effective antiviral short interfering RNAs (siRNAs), we established a plasmid-based test system expressing the mRNA of DsRed2 fused with mRNA sequences of single viral genes, to which certain siRNAs were directed. siRNA sequences were expressed as short hairpin RNA (

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Inhibition of measles virus and subacute sclerosing panencephalitis virus by RNA interference

Cited by 22 publications

References 45 publications

Artificial riboswitches for gene expression and replication control of DNA and RNA viruses

Artificial riboswitches for gene expression and replication control of DNA and RNA viruses

Generation of Recombinant Adenovirus Expressing siRNA against the L mRNA of Measles Virus and Subacute Sclerosing Panencephalitis Virus

Clearance of Measles Virus from Persistently Infected Cells by Short Hairpin RNA

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