Gold Nanorods Induce Innate Immune Response and Reduce Respiratory Syncytial Virus Replication

S. Bawage, P. Tiwari, A. Singh, S. Dixit, S. Pillai, V. Dennis, S. Singh
Alabama State University,
United States

Keywords: RSV, gold nanorods, innate immunity, nanomedicine, nanoparticles

Summary:

Metallic nanoparticles (MNPs) have been used for diverse applications like sensing molecules, diagnosis of cancer, delivery of drugs and vaccines. Among the various MNPs, the gold nanorods (GNR) have been commonly used for such diagnosis and therapeutics usage [1]. Also, the properties of these nanoparticles against bacterial and viral pathogens are gaining interest in recent times. However, there is no clear understanding of the mechanism of inhibition by these nanoparticles. There few studies of MNPs against respiratory viruses like Influenza virus, Parainfluenza virus and Adenovirus [2]. Interestingly, Respiratory syncytial virus (RSV) a significant respiratory pathogen that causes pneumonia and bronchiolitis is minimally explored with respective to MNPs. RSV is a negative, single stranded RNA virus against which there is no effective vaccine or treatment. Here, we show the inhibition of RSV with GNR in HEp-2 cell lines and investigate the antiviral response mediated by the GNRs. At non-cytotoxic dose of 2.5 µg/mL of GNR, the plaque assay showed 82% inhibition of RSV. The GNR exhibited innate antiviral response to counter RSV by orchestrating Toll-like receptor (TLR), NOD-like receptor (NLR) and RIG-I-like receptor (RLR) signalling pathways. The antiviral response for untreated HEp-2 cells, RSV infected cells and GNR-RSV treated cells were studied using real-time PCR (Fig.1). GNR-RSV cells showed significant upregulation of TLR3, cathepsin (CTSS and CTSL) and IRF7 genes. Moreover, 2'-5'-oligoadenylate synthetase 2 gene was upregulated 14-folds, which is response for activation of RNase L that degrades viral RNA. Also, there was upregulation of cytokine gene like IL-8, CXCL-10 and CXCL-11. These antiviral genes interplay led to RSV inhibition mediated by GNR. Our study shows that GNR inhibits RSV and illustrates the molecular events related to the inhibition for the potential antiviral therapeutic applications.