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Research Article

Gold nanorod delivery of an ssRNA immune activator inhibits pandemic H1N1 influenza viral replication

Krishnan V. Chakravarthy, Adela C. Bonoiu, William G. Davis, Priya Ranjan, Hong Ding, Rui Hu, J. Bradford Bowzard, Earl J. Bergey, Jacqueline M. Katz, Paul R. Knight, Suryaprakash Sambhara, and Paras N. Prasad
  1. aDepartment of Anesthesiology and Microbiology and Immunology, State University of New York, Buffalo, NY 14214;
  2. bInfluenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333;
  3. cVeterans Affairs Medical Center, Buffalo, NY 14215; and
  4. dInstitute of Lasers, Photonics, and Biophotonics, State University of New York, Buffalo, NY 14260

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PNAS first published May 24, 2010; https://doi.org/10.1073/pnas.0914561107
Krishnan V. Chakravarthy
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Adela C. Bonoiu
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William G. Davis
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Priya Ranjan
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Hong Ding
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Rui Hu
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J. Bradford Bowzard
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Earl J. Bergey
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Jacqueline M. Katz
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Paul R. Knight
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Suryaprakash Sambhara
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  • For correspondence: pnprasad@acsu.buffalo.edu ssambhara@cdc.gov
Paras N. Prasad
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  • For correspondence: pnprasad@acsu.buffalo.edu ssambhara@cdc.gov
  1. Edited* by Nicholas J. Turro, Columbia University, New York, NY, and approved April 26, 2010 (received for review December 17, 2009)

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Abstract

The emergence of the pandemic 2009 H1N1 influenza virus has become a world-wide health concern. As drug resistance appears, a new generation of therapeutic strategies will be required. Here, we introduce a nanotechnology approach for the therapy of pan-demic and seasonal influenza virus infections. This approach uses gold nanorods (GNRs) to deliver an innate immune activator, pro-ducing a localized therapeutic response. We demonstrated the utility of a biocompatible gold nanorod, GNR-5′PPP-ssRNA nanoplex, as an antiviral strategy against type A influenza virus. In human respiratory bronchial epithelial cells, this nanoplex activated the retinoic acid-inducible gene I (RIG-I) pathogen recognition pathway, resulting in increased expression of IFN-β and other IFN-stimulated genes (ISGs) (e.g., PKR, MDA5, IRF1, IRF7, and MX1). This increase in type I IFN and ISGs resulted in a decrease in the replication of H1N1 influenza viruses. These findings suggest that further evaluation of biocompatible nanoplexes as unique antivirals for treatment of seasonal and pandemic influenza viruses is warranted.

  • antivirals
  • surface plasmon resonance
  • innate immunity
  • interferon
  • retinoic acid-inducible gene I

Footnotes

  • 2To whom correspondence may be addressed. E-mail: pnprasad{at}acsu.buffalo.edu or ssambhara{at}cdc.gov.
  • Author contributions: K.V.C., A.C.B., W.G.D., and S.S. designed research; K.V.C., A.C.B., W.G.D., P.R., R.H., and J.B.B. performed research; H.D. contributed new reagents/analytic tools; K.V.C., A.C.B., W.G.D., J.B.B., J.M.K., P.R.K., S.S., and P.N.P. analyzed data; and K.V.C., A.C.B., W.G.D., P.R., J.B.B., E.J.B., P.R.K., S.S., and P.N.P. wrote the paper.

  • ↵1K.V.C., A.C.B., and W.G.D. contributed equally to this work.

  • The authors declare no conflict of interest.

  • ↵*This Direct Submission article had a prearranged editor.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.0914561107/-/DCSupplemental.

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    Gold nanorod delivery of an ssRNA immune activator inhibits pandemic H1N1 influenza viral replication
    Krishnan V. Chakravarthy, Adela C. Bonoiu, William G. Davis, Priya Ranjan, Hong Ding, Rui Hu, J. Bradford Bowzard, Earl J. Bergey, Jacqueline M. Katz, Paul R. Knight, Suryaprakash Sambhara, Paras N. Prasad
    Proceedings of the National Academy of Sciences May 2010, 200914561; DOI: 10.1073/pnas.0914561107

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    Gold nanorod delivery of an ssRNA immune activator inhibits pandemic H1N1 influenza viral replication
    Krishnan V. Chakravarthy, Adela C. Bonoiu, William G. Davis, Priya Ranjan, Hong Ding, Rui Hu, J. Bradford Bowzard, Earl J. Bergey, Jacqueline M. Katz, Paul R. Knight, Suryaprakash Sambhara, Paras N. Prasad
    Proceedings of the National Academy of Sciences May 2010, 200914561; DOI: 10.1073/pnas.0914561107
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