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      Antiviral Activity of Gold/Copper Sulfide Core/Shell Nanoparticles against Human Norovirus Virus-Like Particles

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          Abstract

          Human norovirus is a leading cause of acute gastroenteritis worldwide in a plethora of residential and commercial settings, including restaurants, schools, and hospitals. Methods for easily detecting the virus and for treating and preventing infection are critical to stopping norovirus outbreaks, and inactivation via nanoparticles (NPs) is a more universal and attractive alternative to other physical and chemical approaches. Using norovirus GI.1 (Norwalk) virus-like particles (VLPs) as a model viral system, this study characterized the antiviral activity of Au/CuS core/shell nanoparticles (NPs) against GI.1 VLPs for the rapid inactivation of HuNoV. Inactivation of VLPs (GI.1) by Au/CuS NPs evaluated using an absorbance-based ELISA indicated that treatment with 0.083 μM NPs for 10 min inactivated ~50% VLPs in a 0.37 μg/ml VLP solution and 0.83 μM NPs for 10 min completely inactivated the VLPs. Increasing nanoparticle concentration and/or VLP-NP contact time significantly increased the virucidal efficacy of Au/CuS NPs. Changes to the VLP particle morphology, size, and capsid protein were characterized using dynamic light scattering, transmission electron microscopy, and Western blot analysis. The strategy reported here provides the first reported proof-of-concept Au/CuS NPs-based virucide for rapidly inactivating human norovirus.

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          Most cited references47

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          Noroviruses: a comprehensive review.

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            Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes.

            Carbon nanotubes are now becoming an important material for use in day to day life because of their unique physical properties. The toxicological impact of these materials has not yet been studied in detail, thereby limiting their use. In the present study, the toxicity of single-walled carbon nanotubes (SWCNT) was assessed in human keratinocyte cells. The results show increased oxidative stress and inhibition of cell proliferation in response to treatment of keratinocytes with SWCNT particles. In addition, the signaling mechanism in keratinocytes upon exposure to SWCNT particles was investigated. Results from the study suggest that SWCNT particles activate NF-kappaB in a dose-dependent manner in human keratinocytes. Further, the mechanism of activation of NF-kappaB was due to the activation of stress-related kinases by SWCNT particles in keratinocytes. In conclusion, these studies show the mechanism of toxicity induced by SWCNT particles.
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              Surrogates for the study of norovirus stability and inactivation in the environment: aA comparison of murine norovirus and feline calicivirus.

              Human noroviruses (NoVs) are the leading cause of food- and waterborne outbreaks of acute nonbacterial gastroenteritis worldwide. As a result of the lack of a mammalian cell culture model for these viruses, studies on persistence, inactivation, and transmission have been limited to cultivable viruses, including feline calicivirus (FCV). Recently, reports of the successful cell culture of murine norovirus 1 (MNV-1) have provided investigators with an alternative surrogate for human NoVs. In this study, we compared the inactivation profiles of MNV-1 to FCV in an effort to establish the relevance of MNV-1 as a surrogate virus. Specifically, we evaluated (i) stability upon exposure to pH extremes; (ii) stability upon exposure to organic solvents; (iii) thermal inactivation; and (iv) surface persistence under wet and dry conditions. MNV-1 was stable across the entire pH range tested (pH 2 to 10) with less than 1 log reduction in infectivity at pH 2, whereas FCV was inactivated rapidly at pH values 9. FCV was more stable than MNV-1 at 56 degrees C, but both viruses exhibited similar inactivation at 63 and 72 degrees C. Long-term persistence of both viruses suspended in a fecal matrix and inoculated onto stainless steel coupons were similar at 4 degrees C, but at room temperature in solution, MNV-1 was more stable than FCV. The genetic relatedness of MNV-1 to human NoVs combined with its ability to survive under gastric pH levels makes this virus a promising and relevant surrogate for studying environmental survival of human NoVs.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 October 2015
                2015
                : 10
                : 10
                : e0141050
                Affiliations
                [1 ]Biomanufacturing Research Institute and Technology Enterprise (BRITE), Department of Pharmaceutical Sciences, North Carolina Central University, Durham, North Carolina, United States of America
                [2 ]Department of Physics, University of Texas at Arlington, Arlington, Texas, United States of America
                Sun Yat-sen University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JJB LY. Performed the experiments: JJB BA CY LM AA. Analyzed the data: JJB BA LY. Contributed reagents/materials/analysis tools: CY LM WC. Wrote the paper: JJB LY.

                Article
                PONE-D-15-21741
                10.1371/journal.pone.0141050
                4608711
                26474396
                e69c5de2-936c-46c6-ac5f-8107a0dc8290
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 19 May 2015
                : 1 October 2015
                Page count
                Figures: 4, Tables: 0, Pages: 14
                Funding
                This study was supported by Agriculture and Food Research Initiative Competitive Grant no. 329 2011-68003-30395 from the USDA National Institute of Food and Agriculture (NIFA).
                Categories
                Research Article
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                All relevant data are within the paper and its Supporting Information files.

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