A Small Interfering RNA Targeting Coxsackievirus B3 Protects Permissive HeLa Cells from Viral Challenge

ABSTRACT We examined the ability of small interfering RNAs (siRNAs) to disrupt infection by coxsackievirus B3 (CVB3). The incorporation of siRNAs dramatically decreased cell death in permissive HeLa cells in parallel with a reduction in viral replication. Three of four siRNAs had potent anti-CVB3 activity. The present study thus demonstrates that the antiviral effect is due to the downregulation of viral replication. In addition, an effective CVB3-specific siRNA had similar antiviral effects in other related enteroviruses possessing sequence homology in the targeted region. Because the CVB3-specific siRNA is effective against other enteroviruses, siRNAs have potential for a universal antienterovirus strategy.

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Small interfering RNA against the 2C genomic region of coxsackievirus B3 exerts potential antiviral effects in permissive HeLa cells

Virus Research ◽

10.1016/j.virusres.2011.09.016 ◽

2012 ◽

Vol 163 (1) ◽

pp. 183-189 ◽

Cited By ~ 6

Author(s):

Ying Luan ◽

Hai-Li Dai ◽

Dan Yang ◽

Lin Zhu ◽

Tie-Lei Gao ◽

...

Keyword(s):

Hela Cells ◽

Small Interfering Rna ◽

Coxsackievirus B3 ◽

Genomic Region ◽

Antiviral Effects ◽

Interfering Rna

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Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06050-12 ◽

2012 ◽

Vol 56 (7) ◽

pp. 3516-3523 ◽

Cited By ~ 5

Author(s):

Jeonghyun Ahn ◽

Ara Ko ◽

Eun Jung Jun ◽

Minah Won ◽

Yoo Kyum Kim ◽

...

Keyword(s):

Rna Interference ◽

Small Interfering Rna ◽

Antiviral Treatment ◽

Coxsackievirus B3 ◽

Hydroxyl Group ◽

Specific Gene ◽

Type I ◽

Antiviral Effects ◽

Direct Demonstration ◽

Interfering Rna

ABSTRACTAntiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases.

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Inhibition of viral replication by small interfering RNA targeting of the foot-and-mouth disease virus receptor integrin β6

Experimental and Therapeutic Medicine ◽

10.3892/etm.2017.4560 ◽

2017 ◽

Vol 14 (1) ◽

pp. 735-742

Author(s):

Na-Na Hu ◽

Wenzhi Zhang ◽

Lina Wang ◽

Yuan-Zhi Wang ◽

Chuang-Fu Chen

Keyword(s):

Viral Replication ◽

Disease Virus ◽

Small Interfering Rna ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Virus Receptor ◽

Mouth Disease Virus ◽

Rna Targeting ◽

Foot And Mouth ◽

Interfering Rna

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Broad-Spectrum Antiviral Activity of Small Interfering RNA Targeting the Conserved RNA Termini of Lassa Virus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01368-06 ◽

2007 ◽

Vol 51 (6) ◽

pp. 2215-2218 ◽

Cited By ~ 23

Author(s):

Stefanie Müller ◽

Stephan Günther

Keyword(s):

Gene Expression ◽

Small Interfering Rna ◽

Lymphocytic Choriomeningitis ◽

Lymphocytic Choriomeningitis Virus ◽

Lassa Virus ◽

Small Interfering Rnas ◽

Rna Targeting ◽

Expression Construct ◽

Interfering Rna ◽

Virus Strains

ABSTRACT Small interfering RNAs targeting the conserved RNA termini upstream of NP and L gene were found to reduce reporter gene expression from Lassa virus replicon and Lassa virus mRNA expression construct and to inhibit replication of different Lassa virus strains, lymphocytic choriomeningitis virus, and Mopeia virus in cell culture.

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Coxsackievirus B3 Infection Induces cyr61 Activation via JNK To Mediate Cell Death

Journal of Virology ◽

10.1128/jvi.78.24.13479-13488.2004 ◽

2004 ◽

Vol 78 (24) ◽

pp. 13479-13488 ◽

Cited By ~ 48

Author(s):

Sun-Mi Kim ◽

Jung-Hyun Park ◽

Sun-Ku Chung ◽

Joo-Young Kim ◽

Ha-Young Hwang ◽

...

Keyword(s):

Cell Death ◽

Hela Cells ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Coxsackievirus B3 ◽

Idiopathic Dilated Cardiomyopathy ◽

Cvb3 Infection ◽

Mediate Cell ◽

Jnk Activation ◽

Interfering Rna

ABSTRACT Coxsackievirus B3 (CVB3), an enterovirus in the Picornavirus family, is the most common human pathogen associated with myocarditis and idiopathic dilated cardiomyopathy. We found upregulation of the cysteine-rich protein gene (cyr61) after CVB3 infection in HeLa cells with a cDNA microarray approach, which is confirmed by Northern blot analysis. It is also revealed that the extracellular amount of Cyr61 protein was increased after CVB3 infection in HeLa cells. cyr61 is an early-transcribed gene, and the Cyr61 protein is secreted into the extracellular matrix. Its function is related to cell adhesion, migration, and neuronal cell death. Here, we show that activation of the cyr61 promoter by CVB3 infection is dependent on JNK activation induced by CVB3 replication and viral protein expression in infected cells. To explore the role of Cyr61 protein in infected HeLa cells, we transiently overexpressed cyr61 and infected HeLa cells with CVB3. This increased CVB3 growth in the cells and promoted host cell death by viral infection, whereas down-expression of cyr61 with short interfering RNA reduced CVB3 growth and showed resistance to cell death by CVB3 infection. In conclusion, we have demonstrated a new role for cyr61 in HeLa cells infected with CVB3, which is associated with the cell death induced by virus infection. These data thus expand our understanding of the physiological functions of cyr61 in virus-induced cell death and provide new insights into the cellular factors involved.

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Small interfering RNA treatment can inhibit Cyprinid herpesvirus 3 associated cell death in vitro

Polish Journal of Veterinary Sciences ◽

10.2478/pjvs-2014-0108 ◽

2014 ◽

Vol 17 (4) ◽

pp. 733-735 ◽

Cited By ~ 3

Author(s):

M. Adamek ◽

G. Rauch ◽

G. Brogden ◽

D. Steinhagen

Keyword(s):

Cell Death ◽

Rna Interference ◽

Small Interfering Rna ◽

Enzyme Synthesis ◽

Small Interfering Rnas ◽

Viral Dna ◽

Cyprinid Herpesvirus 3 ◽

Interfering Rna ◽

Fibroblastic Cells

Abstract A Cyprinid herpesvirus 3 infection of carp induces a disease which causes substantial losses in carp culture. Here we present the use of a possible strategy for the management of the virus infection RNA interference based on small interfering RNAs. As a result of in vitro studies, we found that a mixture of short interfering RNAs specific for viral DNA enzyme synthesis and capsid proteins of the CyHV-3 can be a potential inhibitor of virus replication in fibroblastic cells. This gives the basis for the development of a combinatorial RNA interference strategy to treat CyHV-3 infections.

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