DeRussy Bernadette M, Aylward Madeline A, Fan Zhen, Ray Paresh C, Tandon Ritesh
Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Department of Chemistry and Biochemistry, Jackson State University, 1400 J.R Lynch Street, Jackson, MS 39217, USA.
Sci Rep. 2014 Jul 3;4:5550. doi: 10.1038/srep05550.
Human cytomegalovirus (CMV) is a herpesvirus that causes major health problems in neonates as well as in immunocompromised individuals. At present, a vaccine is not available for CMV infection and the available antiviral drugs suffer from toxicity, poor efficacy and resistance. Here, we chemically conjugated a monoclonal antibody raised against CMV surface glycoprotein (gB) with gold nanoparticles (GNP) and characterized the potential of this gB-GNP conjugate for antiviral activity against CMV. The gB-GNP blocks viral replication, virus-induced cytopathogenic effects and virus spread in cell culture without inducing cytotoxicity. High concentrations of gB-GNP that coat the surface of virus particles block virus entry, whereas lower concentrations block a later stage of virus life cycle. Also, cells treated with gB-GNP gain resistance to CMV infection. In addition, infected cells when bound to gB-GNP can be selectively lysed after exposing them to specific wavelength of laser (nanophotothermolysis). Thus, we have not only designed a potential antiviral strategy that specifically blocks CMV infection at multiple stages of virus life cycle, but we have also characterized a technique that can potentially be useful in eliminating CMV infected cells from donor tissue during transplant or transfusion.
人巨细胞病毒(CMV)是一种疱疹病毒,可在新生儿以及免疫功能低下的个体中引发严重的健康问题。目前,尚无针对CMV感染的疫苗,现有的抗病毒药物存在毒性、疗效不佳和耐药性等问题。在此,我们将一种针对CMV表面糖蛋白(gB)的单克隆抗体与金纳米颗粒(GNP)进行化学偶联,并表征了这种gB-GNP偶联物对CMV的抗病毒活性潜力。gB-GNP可阻断病毒复制、病毒诱导的细胞病变效应以及病毒在细胞培养中的传播,且不会诱导细胞毒性。高浓度的gB-GNP覆盖病毒颗粒表面可阻断病毒进入,而较低浓度则阻断病毒生命周期的后期阶段。此外,用gB-GNP处理的细胞对CMV感染具有抗性。另外,感染的细胞与gB-GNP结合后,在暴露于特定波长的激光(纳米光热解)后可被选择性裂解。因此,我们不仅设计了一种潜在的抗病毒策略,可在病毒生命周期的多个阶段特异性阻断CMV感染,而且还表征了一种技术,该技术可能有助于在移植或输血过程中从供体组织中消除CMV感染的细胞。