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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010-06, Vol.107 (22), p.10172-10177
• Main Authors: Chakravarthy, Krishnan V, Bonoiu, Adela C, Davis, William G, Ranjan, Priya, Ding, Hong, Hu, Rui, Bowzard, J. Bradford, Bergey, Earl J, Katz, Jacqueline M, Knight, Paul R, Sambhara, Suryaprakash, Prasad, Paras N
• Format: Article
• Language: English
• Subjects: Antiviral Agents - administration & dosage; Antiviral drugs; Antivirals; b-Interferon; Biological Sciences; Cell Line; DEAD Box Protein 58; DEAD-box RNA Helicases - metabolism; Drug Delivery Systems; Drug resistance; Epithelial cells; Gene expression; Gold; H1N1 subtype influenza A virus; Humans; Immunity, Innate - drug effects; Immunology; Infection; Infections; Influenza; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - physiology; Influenza virus; Interferon; Interferon regulatory factor 1; Interferon regulatory factor 7; Interferon-beta - metabolism; Medical treatment; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - ultrastructure; Microscopy, Electron, Transmission; Myxovirus resistance proteins; Nanoparticles; Nanorods; Nanotechnology; Nanotubes - ultrastructure; Orthomyxoviridae; Pandemics; Pathogens; Receptors, Immunologic; Replication; Ribonucleic acid; RNA; RNA - administration & dosage; RNA - immunology; Signal Transduction - drug effects; Surface Plasmon Resonance; Swine flu; Virus Replication - drug effects; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0914561107

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.