Monitoring the in vivo Dynamics of Avian Influenza Viruses Using Bioorthogonal-Conjugated Near-Infrared Quantum Dots

May 16, 2014     Email"> PrintText Size

Highly pathogenic avian influenza A viruses are emerging pandemic threats that have caused several outbreaks with high mortality in human beings in the past decades. The infection of avian influenza viruses, such as subtype H5 and H7, could cause a series of severe respiratory and extra-respiratory complications, both of which are directly associated with viral loading and dissemination in tissues. Understanding the route and pathogenesis of avian influenza viral infection is extremely important for developing prophylactic and therapeutic strategies against viral infections. Although the studies using cell cultures have made a significant contribution to exploring the pathogenesis of avian influenza viruses, it is highly desirable to track the in vivo dynamics of viral infection in order to further dissect the interactions between the virus and the host.  

Viral particle labeling with quantum dots (QDs) has emerged as an effective strategy for virus tracking. Compared with conventional dyes, QDs demonstrate bright photoluminescence, broad size-tunable emission spectrum, and photochemical stability and have been successfully applied for single-virus tracking in vitro. Especially, QDs with near-infrared (NIR) spectrum from 700 to 900 nm have attracted intense attention due to the ability of deep-tissue imaging in this wavelength range (Adv. Funct. Mater, 2014, DOI: 10.1002/adfm.201304225). Bioorthogonal chemistry, a biocompatible chemical reaction that can occur in the presence of other rich chemical functionalities found in biological systems without interacting or interfering with native biochemical processes, allowed a wide range of bioactive molecules to be specifically labeled in living organisms. Our previous studies reported that the copper-free click chemistry was a simple, effective, and bioorthogonal strategy for live viral labeling and did not significantly affect viral infectivity (J. Am. Chem. Soc., 2012, 134 (20), 8388–8391).   

PAN Hong et al. from MA Yifan research group (SIAT) and ZHANG Pengfei et al. from CAI Lintao research group (SIAT) collaborated and labeled avian influenza H5N1 pseudotype virus (H5N1p) with NIR QDs by bioorthogonal reaction, and dynamically monitored the respiratory infection of QD-labeled H5N1p (QD-H5N1p) in mice using an in vivo imaging system. QD-H5N1p demonstrated bright and sustained fluorescent signals in mouse lung tissues, which were strongly correlated with the severity of viral infection that was verified by lung histology. We also explored the potential application of QD-H5N1p for antiviral drug evaluation. The results showed that the administration of the antivrial agents oseltamivir carboxylate and mouse antiserum significantly affected the in vivo dynamics of QD-H5N1p infection, which could be directly quantified by measuring fluorescent signals and cadmium (Cd) concentration of virus-conjugated QDs using Inductively coupled plasma/optical emission spectrometry (ICP-OES). The research results titled “Noninvasive Visualization of Respiratory Viral Infection Using Bioorthogonal Conjugated Near-Infrared-Emitting Quantum Dots” have been recently published online on May 5 in ACS NANO (IF=12.062). The presented research was financially supported by the National Basic Research Program of China (973 Program), the National Natural Science Foundation of China, the ‘‘Hundred Talents Program’’ of Chinese Academy of Sciences, Science and Technology Foundation of Guangdong Province of China, Guangdong Innovation Reasearch Team of Low-cost Healthcare and SIAT Innovation Program for Excellent Young Researchers.  

The research group, led by Prof. CAI Lintao, carries out world leading research on a range of biomedical nanotechnology including studying multifunctional and nanostructured composite materials, providing highly sensitive and bioorthogonal labeling method for in vivo imaging and molecular diagnosis in nanoscale and single molecular level, exploring new device concepts and self-assembly techniques for the development of biomedical nanodevices and sensors for biosensing, and other applications. The research group, led by Prof. MA Yifan, carries out world leading research that mostly focuses on nanoparticle-based adjuvant and vaccine delivery systems immune regulation mechanism of nanomaterials, in vivo tracking of virus and cell using NIR imaging technology, as well as cancer immunotherapy. 

 

Schematic Illustration of the Bioorthogonal Labeling and in vivo Imaging of Viruses Using Conjugated Near-Infrared Quantum Dots
(Image by SIAT)

 

Contact:
CAI Lintao
Ph.D., Professor
Institute of Biomedicine and Biotechnology
Shenzhen Institutes of Advanced Technology
Chinese Academy of Sciences
Shenzhen 518055, Guangdong (P. R. China)
Telephone: +86-755-86392210　 E-mail: lt.cai@siat.ac.cn
 
MA Yifan
Ph.D., Professor
Institute of Biomedicine and Biotechnology
Shenzhen Institutes of Advanced Technology
Chinese Academy of Sciences
Shenzhen 518055, Guangdong (P. R. China)
Telephone: +86-755-86585216　 E-mail: yf.ma@siat.ac.cn