The utility of siRNA transcripts produced by RNA polymerase i in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses

McCown, Matthew F.; Diamond, Michael S.; Pekosz, Andrew

doi:10.1016/s0042-6822(03)00341-6

Cited by 79 publications

(68 citation statements)

References 63 publications

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“…After sequencing, pcDNA-E or the parent vector, pcDNA3.1, was transfected into MC57GL cells by a previously described protocol (50). Fortyeight hours after transfection, cells were selected with Dulbecco modified Eagle medium (DMEM) supplemented with zeocin (0.2 mg/ml).…”

Section: Quantitation Of Virus Burden From Micementioning

confidence: 99%

Role of CD8⁺T Cells in Control of West Nile Virus Infection

Shrestha

Diamond

2004

J Virol

365

391

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Infection with West Nile virus (WNV) causes fatal encephalitis more frequently in immunocompromised humans than in those with a healthy immune system. Although a complete understanding of this increased risk remains unclear, experiments with mice have begun to define how different components of the adaptive and innate immune response function to limit infection. Previously, we demonstrated that components of humoral immunity, particularly immunoglobulin M (IgM) and IgG, have critical roles in preventing dissemination of WNV infection to the central nervous system. In this study, we addressed the function of CD8 ؉ T cells in controlling WNV infection. Mice that lacked CD8 ؉ T cells or classical class Ia major histocompatibility complex (MHC) antigens had higher central nervous system viral burdens and increased mortality rates after infection with a low-passage-number WNV isolate. In contrast, an absence of CD8 ؉ T cells had no effect on the qualitative or quantitative antibody response and did not alter the kinetics or magnitude of viremia. In the subset of CD8؉ -T-cell-deficient mice that survived initial WNV challenge, infectious virus was recovered from central nervous system compartments for several weeks. Primary or memory CD8؉ T cells that were generated in vivo efficiently killed target cells that displayed WNV antigens in a class I MHC-restricted manner. Collectively, our experiments suggest that, while specific antibody is responsible for terminating viremia, CD8 ؉

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Section: Quantitation Of Virus Burden From Micementioning

confidence: 99%

Role of CD8⁺T Cells in Control of West Nile Virus Infection

Shrestha

Diamond

2004

J Virol

365

391

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“…Because siRNAs confer transient interference of gene expression in a sequence-specific manner, they represent a new class of molecules that are likely to have significant medical applications (14,15). siRNAs have been shown to inhibit virus infection if they are transfected into cultured cells by electroporation or by using cationic lipids (16)(17)(18)(19)(20). Similarly, we have previously shown that siRNAs specific for conserved regions of the influenza A virus genes can inhibit virus production profoundly in cultured cells and embryonated chicken eggs (21).…”

mentioning

confidence: 99%

Inhibition of influenza virus production in virus-infected mice by RNA interference

Filip

Bai

et al. 2004

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

420

345

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Influenza A virus infection is a major source of morbidity and mortality worldwide. Because the effectiveness of existing vaccines and antiviral drugs is limited, development of new treatment modalities is needed. Here, we show that short interfering RNAs (siRNAs) specific for conserved regions of influenza virus genes can prevent and treat influenza virus infection in mice. Virus production in lungs of infected mice is reduced by siRNAs given either before or after initiating virus infection, by using slow i.v. administration of small volumes containing siRNAs in complexes with a polycation carrier. Similar effects also are observed when mice are given DNA vectors i.v. or intranasally, from which siRNA precursors can be transcribed. Development of delivery systems that may be compatible with human use demonstrates the potential utility of siRNAs for prophylaxis and therapy of influenza virus infections in humans.

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“…These findings raised the possibility that RNAi could inhibit viral gene expression and protect cells from viral infection. Subsequently, a number of studies demonstrated inhibition of replication of RNA viruses in vitro by RNAi (9)(10)(11), including HIV (12,13), polio virus (14), hepatitis C virus (15,16), West Nile virus (17), and influenza virus (17,18). Moreover, a number of groups demonstrated effective silencing of both transgene and endogenous gene expression in vivo (19)(20)(21)(22)(23)(24)(25).…”

mentioning

confidence: 99%

Protection against lethal influenza virus challenge by RNA interferencein vivo

Tompkins

Tumpey

et al. 2004

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

356

294

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Influenza virus infection is responsible for hundreds of thousands of deaths annually. Current vaccination strategies and antiviral drugs provide limited protection; therefore, new strategies are needed. RNA interference is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with small interfering RNAs (siRNAs) specific for highly conserved regions of the nucleoprotein or acidic polymerase inhibits influenza A virus replication in vivo. Delivery of these siRNAs significantly reduced lung virus titers in infected mice and protected animals from lethal challenge. This protection was specific and not mediated by an antiviral IFN response. Moreover, influenza-specific siRNA treatment was broadly effective and protected animals against lethal challenge with highly pathogenic avian influenza A viruses of the H5 and H7 subtypes. These results indicate that RNA interference is promising for control of influenza virus infection, as well as other viral infections.

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The utility of siRNA transcripts produced by RNA polymerase i in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses

Cited by 79 publications

References 63 publications

Role of CD8⁺T Cells in Control of West Nile Virus Infection

Role of CD8⁺T Cells in Control of West Nile Virus Infection

Inhibition of influenza virus production in virus-infected mice by RNA interference

Protection against lethal influenza virus challenge by RNA interferencein vivo

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The utility of siRNA transcripts produced by RNA polymerase i in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses

Cited by 79 publications

References 63 publications

Role of CD8+T Cells in Control of West Nile Virus Infection

Role of CD8+T Cells in Control of West Nile Virus Infection

Inhibition of influenza virus production in virus-infected mice by RNA interference

Protection against lethal influenza virus challenge by RNA interferencein vivo

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Product

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Role of CD8⁺T Cells in Control of West Nile Virus Infection

Role of CD8⁺T Cells in Control of West Nile Virus Infection