Effective small interfering RNAs targeting matrix and nucleocapsid protein gene inhibit influenza A virus replication in cells and mice

Zhou, Hongbo; Jin, Meilin; Yu, Zhengjun; Xu, Xiaojuan; Peng, Yaping; Wu, Haiya; Liu, Jinlin; Liu, Hu; Cao, Shengbo; Chen, Huanchun

doi:10.1016/j.antiviral.2007.07.002

Cited by 75 publications

(53 citation statements)

References 15 publications

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“…Replication of IAV and levels of M1 RNAs were significantly reduced in cells transfected with shRNAs that decreased the virus titer. These results are in coincidence with previous findings of other authors and confirm that IAV replication is inhibited in a gene specific manner (Hui et al, 2004;Zhou et al, 2007;Švančarová et al, 2015).…”

Section: Discussionsupporting

confidence: 51%

“…Transfection of cells with some M1-specific siRNAs resulted in reduced replication of IAV (Ge et al, 2003(Ge et al, , 2004Hui et al, 2004;Zhou et al, 2007). In the present study, we demonstrated the effect of shRNAs targeting the M gene on the treatment of an established IAV infection.…”

Section: Introductionmentioning

confidence: 63%

“…The protection rate was calculated as the number of surviving animals/total number of animals x 100% (n = 2x4) at each time point. later (Ge et al, 2003;Hui et al, 2004;Zhou et al, 2004Zhou et al, , 2007Zhiqiang et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Induction of interferon lambda in influenza a virus infected cells treated with shRNAs against M1 transcript

Švančarová¹,

Svetlíková²,

Betáková³

2015

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Summary. -RNA interference (RNAi) represents a form of post-transcriptional gene silencing mediated by small interfering RNAs (siRNA) and provides a powerful tool to specifically inhibit viral infection. To investigate therapeutic capacity of siRNAs targeting M gene, six vectors with U1-short hairpin RNA (shRNA) expression system were prepared and tested in infected cells and animals. In infected cells, three of six shRNAs targeting M1 gene significantly (P <0,01) reduced the virus titer to 66%, 45% or 21%, respectively. Replication of IAV and levels of M1 RNAs were significantly reduced in the cells transfected with shRNAs, which decreased the virus titer. IFN-α/β altered in shRNAs-treated cells. The level of IFN-λ (type III interferon) mRNA was significantly increased in the infected cells treated with shM22, shM349, shM522, and (type I interferon) as well as IP-10 (type II interferon) mRNAs were not significantly their mixtures. The increased level of IFN-λ mRNA corresponded to significantly increased level of RIG-1 mRNA. shRNAs inhibited influenza virus infection in a gene-specific manner in co-operation with IFN-λ. Some constructs targeting the M1 transcript prolonged the survival of infected mice.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 63%

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Induction of interferon lambda in influenza a virus infected cells treated with shRNAs against M1 transcript

Švančarová¹,

Svetlíková²,

Betáková³

2015

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“…Nevertheless, this technology has been exploited as a potential antiviral strategy to inhibit the replication of several RNA and DNA animal viruses (Haasnoot et al 2003). Impressive results using tissue culture models have been achieved against various cancer cells, targeting oncogenes, human immunodeficiency virus (HIV), influenza and polioviruses by targeting viral genes (Jacque et al 2002;Zhou et al 2007;Gitlin et al 2002). In-vitro studies on the inhibitory effect of gene specific siRNA on FMDV replication in BHK-21 cells and mouse models has been investigated (Mohapatra et al 2005).…”

Section: Introductionmentioning

confidence: 99%

The plasmid constructs producing shRNA corresponding to the conserved 3D polymerase of Foot and Mouth Disease virus protects guinea pigs against challenge virus

et al. 2008

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RNA interference (RNAi) has been used as an effective antiviral strategy for its specific silencing of viral gene expression in mammalian cells. In this study, shRNA targeting two regions of Foot and Mouth Disease Virus (FMDV) i.e. 3D and 5'UTR which are very essential in virus replication were evaluated. The constructs were made using h7K RNA polymerase III promoter. We investigated in vivo inhibitory effect of shRNA on FMDV replication in BHK-21 cells and guinea pigs. The results showed that transfection of 3D shRNA could reduce virus growth by three folds when cells were challenged with 10(2) TCID(50) of FMDV. Pretreated guinea pigs with 3DshRNA were protected 80% with 10(3) GPID(50) of FMDV. As a first report in guinea pigs which are recognized animal model for FMD vaccine potency testing, the study suggests that shRNA could be a viable therapeutic approach to control severity of FMD infection and spread.

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“…Double stranded RNA molecules can cause sequencespecific translational inhibition, while synthetic small interfering RNAs (siRNAs) have inhibited influenza virus replication when transfected into cells before or after viral challenge [41,48]. In a recent publication, Zhou et al developed M2-and NA-specific siRNAs that not only inhibited influenza A in transfected cells but also produced a 16-50 fold reduction in mouse lung titers following intravenous injection [48]. This strategy has been tested with promising results against pathogenic avian influenza A viruses of the H5 and H7 subtypes in mice using an intranasal delivery system with a cationic transfection reagent [49].…”

Section: Current Pharmacotherapy and Drug Developmentmentioning

confidence: 99%

Pandemic and seasonal influenza: therapeutic challenges

Memoli

Morens

Taubenberger

2008

Drug Discovery Today

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Influenza A viruses cause significant morbidity and mortality annually, and the threat of a pandemic underscores the need for new therapeutic strategies. Here we briefly discuss novel antiviral agents under investigation, the limitations of current antiviral therapy and stress the importance of secondary bacterial infections in seasonal and pandemic influenza. Additionally, the lack of new antibiotics available to treat increasingly drug resistant organisms such as methicillin-resistant Staphylococcus aureus, pneumococci, Acinetobacter, extended spectrum beta-lactamase producing gram negative bacteria and Clostridium difficile is highlighted as an important component of influenza treatment and pandemic preparedness. Addressing these problems will require a multidisciplinary approach, which includes the development of novel antivirals and new antibiotics, as well as a better understanding of the role secondary infections play on the morbidity and mortality due to influenza infection.

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Effective small interfering RNAs targeting matrix and nucleocapsid protein gene inhibit influenza A virus replication in cells and mice

Cited by 75 publications

References 15 publications

Induction of interferon lambda in influenza a virus infected cells treated with shRNAs against M1 transcript

Induction of interferon lambda in influenza a virus infected cells treated with shRNAs against M1 transcript

The plasmid constructs producing shRNA corresponding to the conserved 3D polymerase of Foot and Mouth Disease virus protects guinea pigs against challenge virus

Pandemic and seasonal influenza: therapeutic challenges

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