Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
ACS Nano. 2014 Jun 24;8(6):5468-77. doi: 10.1021/nn501028b. Epub 2014 May 9.
Highly pathogenic avian influenza A viruses are emerging pandemic threats in human beings. Monitoring the in vivo dynamics of avian influenza viruses is extremely important for understanding viral pathogenesis and developing antiviral drugs. Although a number of technologies have been applied for tracking viral infection in vivo, most of them are laborious with unsatisfactory detection sensitivity. Herein we labeled avian influenza H5N1 pseudotype virus (H5N1p) with near-infrared (NIR)-emitting QDs by bioorthogonal chemistry. The conjugation of QDs onto H5N1p was highly efficient with superior stability both in vitro and in vivo. Furthermore, QD-labeled H5N1p (QD-H5N1p) demonstrated bright and sustained fluorescent signals in mouse lung tissues, allowing us to visualize respiratory viral infection in a noninvasive and real-time manner. The fluorescence signals of QD-H5N1p in lung were correlated with the severity of virus infection and significantly attenuated by antiviral agents, such as oseltamivir carboxylate and mouse antiserum against H5N1p. The biodistribution of QD-H5N1p in lungs and other organs could be easily quantified by measuring fluorescent signals and cadmium concentration of virus-conjugated QDs in tissues. Hence, virus labeling with NIR QDs provides a simple, reliable, and quantitative strategy for tracking respiratory viral infection and for antiviral drug screening.
高致病性禽流感病毒是人类中出现的具有大流行威胁的病毒。监测禽流感病毒在体内的动态变化对于了解病毒发病机制和开发抗病毒药物非常重要。尽管已经应用了许多技术来跟踪体内的病毒感染,但大多数技术都很繁琐,检测灵敏度也不尽如人意。在此,我们通过生物正交化学方法对禽流感 H5N1 假型病毒(H5N1p)进行了近红外(NIR)发射量子点(QD)标记。QD 与 H5N1p 的缀合具有很高的效率,无论是在体外还是体内都具有优异的稳定性。此外,QD 标记的 H5N1p(QD-H5N1p)在小鼠肺组织中表现出明亮且持续的荧光信号,使我们能够以非侵入性和实时的方式可视化呼吸道病毒感染。QD-H5N1p 在肺部的荧光信号与病毒感染的严重程度相关,并且可以通过抗病毒药物(如奥司他韦羧酸盐和针对 H5N1p 的小鼠抗血清)显著减弱。通过测量组织中病毒结合的 QD 的荧光信号和镉浓度,可以轻松定量 QD-H5N1p 在肺部和其他器官中的分布。因此,用近红外 QD 标记病毒为跟踪呼吸道病毒感染和筛选抗病毒药物提供了一种简单、可靠和定量的策略。