Rabies Virus Pseudotyped with CVS-N2C Glycoprotein as a Powerful Tool for Retrograde Neuronal Network Tracing

• DOI: 10.1007/s12264-019-00423-3
• Publication Date: 2019-08-23T08:02:53Z
• Authors: Xutao Zhu; Kunzhang Lin; Qing Liu; Xinpei Yue; Huijie Mi; Xiaoping Huang; Xiaobin He; Ruiqi Wu; Danhao Zheng; Dong Wei; Liangliang Jia; Weilin Wang; Anne Manyande; Jie Wang; Zhijian Zhang; Fuqiang Xu
• Keywords: Male; 0303 health sciences; Genetic Vectors; Ventral Tegmental Area; health; Cell Line; 3. Good health; Mice, Inbred C57BL; Neuroanatomical Tract-Tracing Techniques; Mice; Viral Proteins; 03 medical and health sciences; Rabies virus; Cricetinae; Dentate Gyrus; Animals; Nerve Net; Glycoproteins

Efficient viral vectors for mapping and manipulating long-projection neuronal circuits are crucial in structural and functional studies of the brain. The SAD strain rabies virus with the glycoprotein gene deleted pseudotyped with the N2C glycoprotein (SAD-RV(ΔG)-N2C(G)) shows strong neuro-tropism in cell culture, but its in vivo efficiency for retrograde gene transduction and neuro-tropism have not been systematically characterized. We compared these features in different mouse brain regions for SAD-RV-N2C(G) and two other widely-used retrograde tracers, SAD-RV(ΔG)-B19(G) and rAAV2-retro. We found that SAD-RV(ΔG)-N2C(G) enhanced the infection efficiency of long-projecting neurons by ~10 times but with very similar neuro-tropism, compared with SAD-RV(ΔG)-B19(G). On the other hand, SAD-RV(ΔG)-N2C(G) had an infection efficiency comparable with rAAV2-retro, but a more restricted diffusion range, and broader tropism to different types and regions of long-projecting neuronal populations. These results demonstrate that SAD-RV(ΔG)-N2C(G) can serve as an effective retrograde vector for studying neuronal circuits.