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

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.

Optogenetic and Chemogenetic Approaches for Studying Astrocytes and Gliotransmitters

“…A number of studies have employed virally mediated expression of opsins to manipulate astrocytes, despite the possibility of inducing reactive gliosis as a result of viral infection [116]. This approach appears to be as successful as using transgenic mouse lines.…”

Optogenetic Approaches for Controlling Seizure Activity

“…Viral vectors encoding opsin genes are produced in vitro and are subsequently injected into the brain where they can transduce target cells. The cell tropism of these viral vectors can vary depending on the class or serotype of the vector and should thus be chosen carefully [27–31]. Cell-type specific expression of opsins can be further achieved by utilizing an appropriate promoter driving transgene expression.…”

Pdlim4 is essential for CCR7‐JNK–mediated dendritic cell migration and F‐actin–related dendrite formation

“…5A). Additionally, to assess the cell size and formation of dendrites after LPS stimulation for 24 h, we applied a Sholl analysis method (23) to DCs (Fig. 5B).…”