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Cross-Protective Effect of Antisense Oligonucleotide Developed Against the Common 3′ NCR of Influenza A Virus Genome

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Abstract

The influenza A virus (IAV) has eight segmented single-stranded RNA genome containing a common and evolutionarily conserved non-coding region (NCRs) at 5′ and 3′ ends that are important for the virus replication. In this study, we designed an antisense oligonucleotide against the 3′ NCR of vital segments of the IAV genome to inhibit its replication. The results demonstrated that the co-transfection of Madine Darby Canine Kidney (MDCK) cells with the antisense oligonucleotide and the plasmids encoding the viral genes led to the down-regulation of the viral gene expression. The designed antisense molecules reduced the cytopathic effect caused by A/PR/8/34 (H1N1), A/Udorn/307/72 (H3N2), and A/New Caledonia/20/99 (H1N1) strains of IAV for almost 48 h. Furthermore, the intra-venous delivery of this oligonucleotide significantly reduced the viral titers in the lungs of infected mice and protected the mice from lethal effects of all the strains of influenza virus. The study demonstrated that the antisense oligonucleotide designed against the NCR region inhibits the expression of the viral genome. The decrease of the cytopathic effect in the MDCK cells and increase in survival of mice confirmed the reduction of virus multiplication and pathogenesis in the presence of antisense oligonucleotide. Thus, we demonstrate that a single antisense oligonucleotide is capable of providing protection against more than one strains of the IAV.

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Abbreviations

Dz:

DNAzymes

Rz:

Ribozyme

AS:

Antisense

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Acknowledgments

We thank the help rendered by our laboratory staff for successful completion of the study.

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Authors and Affiliations

  1. Department of Respiratory Virology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India

    Prashant Kumar, Binod Kumar, Roopali Rajput, Latika Saxena & Madhu Khanna

  2. Virology Laboratory-II, National Institute of Immunology, New Delhi, 110067, India

    Akhil C. Banerjea

Authors
  1. Prashant Kumar
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  2. Binod Kumar
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  3. Roopali Rajput
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  4. Latika Saxena
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  5. Akhil C. Banerjea
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  6. Madhu Khanna
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Correspondence to Madhu Khanna.

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Kumar, P., Kumar, B., Rajput, R. et al. Cross-Protective Effect of Antisense Oligonucleotide Developed Against the Common 3′ NCR of Influenza A Virus Genome. Mol Biotechnol 55, 203–211 (2013). https://doi.org/10.1007/s12033-013-9670-8

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