Inhibition of A/Human/Hubei/3/2005 (H3N2) influenza virus infection by silver nanoparticles in vitro and in vivo

Abstract

Dongxi Xiang,1 Yang Zheng,2 Wei Duan,1 Xiujing Li,3 Jianjian Yin,3 Sarah Shigdar,1 Michael Liam O’Connor,1 Manju Marappan,1 Xiaojuan Zhao,4 Yingqiu Miao,3 Bin Xiang,5 Conglong Zheng31School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia; 2Department of Pharmacology, Osaka University, Osaka, Japan; 3Department of Biology, Medical College, Dalian University, Liaoning, People’s Republic of China; 4Department of Gynaecology and Obstetrics, Qingdao Central Hospital, Shandong, People’s Republic of China; 5Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Liaoning, People’s Republic of ChinaAbstract: Silver nanoparticles (AgNPs) have attracted much attention as antimicrobial agents and have demonstrated efficient inhibitory activity against various viruses, including human immunodeficiency virus, hepatitis B virus, and Tacaribe virus. In this study, we investigated if AgNPs could have antiviral and preventive effects in A/Human/Hubei/3/2005 (H3N2) influenza virus infection. Madin-Darby canine kidney cells infected with AgNP-treated H3N2 influenza virus showed better viability (P<0.05 versus influenza virus control) and no obvious cytopathic effects compared with an influenza virus control group and a group treated with the solvent used for preparation of the AgNPs. Hemagglutination assay indicated that AgNPs could significantly inhibit growth of the influenza virus in Madin-Darby canine kidney cells (P<0.01 versus the influenza virus control). AgNPs significantly reduced cell apoptosis induced by H3N2 influenza virus at three different treatment pathways (P<0.05 versus influenza virus control). H3N2 influenza viruses treated with AgNPs were analyzed by transmission electron microscopy and found to interact with each other, resulting in destruction of morphologic viral structures in a time-dependent manner in a time range of 30 minutes to 2 hours. In addition, intranasal AgNP administration in mice significantly enhanced survival after infection with the H3N2 influenza virus. Mice treated with AgNPs showed lower lung viral titer levels and minor pathologic lesions in lung tissue, and had a marked survival benefit during secondary intranasal passage in vivo. These results provide evidence that AgNPs have beneficial effects in preventing H3N2 influenza virus infection both in vitro and in vivo, and demonstrate that AgNPs can be used as potential therapeutics for inhibiting outbreaks of influenza.Keywords: silver nanoparticles, influenza virus, H3N2, antiviral activity