Articles

Article

Original Article

Exp Neurobiol 2016; 25(1): 48-54

Published online February 29, 2016

https://doi.org/10.5607/en.2016.25.1.48

© The Korean Society for Brain and Neural Sciences

Differential Cellular Tropism of Lentivirus and Adeno-Associated Virus in the Brain of Cynomolgus Monkey

Heeyoung An1,2, Doo-Wan Cho3, Seung Eun Lee1, Young-Su Yang3,Su-Cheol Han3* and C. Justin Lee1,2*

1Center for Neuroscience and Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, 2KU-KIST School of Converging Science and Technology, Korea University, Seoul 02841, 3General Toxicology Research Center, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, KRICT, Jeongeup 56212, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-63-570-8520, 82-2-958-6940, FAX: 82-63-570-8999, 82-2-958-6937
Su-Cheol Han e-mail: vethansc@kitox.re.kr,
C. Justin Lee e-mail: cjl@kist.re.kr

Received: January 29, 2016; Revised: February 10, 2016; Accepted: February 11, 2016

Abstract

Many researchers are using viruses to deliver genes of interest into the brains of laboratory animals. However, certain target brain cells are not easily infected by viruses. Moreover, the differential tropism of different viruses in monkey brain is not well established. We investigated the cellular tropism of lentivirus and adeno-associated virus (AAV) toward neuron and glia in the brain of cynomolgus monkeys (Macaca fascularis). Lentivirus and AAV were injected into putamen of the monkey brain. One month after injection, monkeys were sacrificed, and then the presence of viral infection by expression of reporter fluorescence proteins was examined. Tissues were sectioned and stained with NeuN and GFAP antibodies for identifying neuronal cells or astrocytes, respectively, and viral reporter GFP-expressing cells were counted. We found that while lentivirus infected mostly astrocytes, AAV infected neurons at a higher rate than astrocytes. Moreover, astrocytes showed reactiveness when cells were infected by virus, likely due to virus-mediated neuroinflammation. The Sholl analysis was done to compare the hypertrophy of infected and uninfected astrocytes by virus. The lentivirus infected astrocytes showed negligible hypertrophy whereas AAV infected astrocytes showed significant changes in morphology, compared to uninfected astrocytes. In the brain of cynomolgus monkey, lentivirus shows tropism for astrocytes over neurons without much reactivity in astrocytes, whereas AAV shows tropism for neurons over glial cells with a significant reactivity in astrocytes. We conclude that AAV is best-suited for gene delivery to neurons, whereas lentivirus is the best choice for gene delivery to astrocytes in the brain of cynomolgus monkeys.

Keywords: virus tropism, lentivirus, AAV, monkey, neuron, astrocyte