title: Gold nanorod delivery of an ssRNA immune activator inhibits pandemic H1N1 influenza viral replication.
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-beta 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.
authors.affiliation: Department of Anesthesiology and Microbiology and Immunology, State University of New York, Buffalo, NY 14214, USA.
authors.forename: Krishnan V
authors.initials: KV
authors.lastname: Chakravarthy
authors.forename: Adela C
authors.initials: AC
authors.lastname: Bonoiu
authors.forename: William G
authors.initials: WG
authors.lastname: Davis
authors.forename: Priya
authors.initials: P
authors.lastname: Ranjan
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.forename: J Bradford
authors.initials: JB
authors.lastname: Bowzard
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Bergey
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D016503:Drug Delivery Systems; D006046:Gold; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016899:Interferon-beta / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D043942:Nanotubes / Q000648:ultrastructure; D012313:RNA / Q000008:administration & dosage* / Q000276:immunology; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000187:drug effects; D020349:Surface Plasmon Resonance; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011971:Receptors, Immunologic; D012313:RNA; D006046:Gold; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases