Differential cellular tropism of lentivirus and adeno-associated virus in the brain of cynomolgus monkey

Heeyoung An, Doo Wan Cho, Seung Eun Lee, Young Su Yang, Su Cheol Han, Changjoon Lee

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalExperimental Neurobiology
Volume25
Issue number1
DOIs
Publication statusPublished - 2016 Feb 1

Keywords

  • AAV
  • Astrocyte
  • Lentivirus
  • Monkey
  • Neuron
  • Virus tropism

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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