Development of rhesus macaque astrocyte cell lines supporting infection with a panel of viruses

PLoS One. 2024 May 14;19(5):e0303059. doi: 10.1371/journal.pone.0303059. eCollection 2024.

Abstract

Non-human primate (NHP)-based model systems are highly relevant for biomedical research. However, only few NHP cell lines are available and the generation of additional cell lines is an urgent need to help in the refinement and replacement of these models. Using lentiviral transduction of c-Fos, we established cell lines from the brain of rhesus macaques (Macaca mulatta). Transcriptome analysis revealed that these cell lines are closely related to astrocytes, which was confirmed by immunoblot and immunofluorescence microscopy detecting expression of the astrocyte marker glial fibrillary acidic protein (GFAP). Quantitative real-time PCR (qRT-PCR) demonstrated that major pathways of the interferon (IFN) system are intact. Using retroviral pseudotypes we found that the cell lines are susceptible to entry driven by the glycoproteins of vesicular stomatitis virus (VSV), lymphocytic choriomeningitis virus (LCMV) and to a lesser extent influenza A virus (IAV). Finally, these cells supported growth of Zika virus (ZIKV) and Papiine alphaherpesvirus 2 (PaHV2). In summary, we developed IFN-responsive cell lines from the rhesus macaque brain that allowed entry driven by several viral glycoproteins and were permissive to infection with ZIKV and a primate simplexvirus. These cell lines will be useful for efforts to analyze neurotropic viral infections in rhesus macaque models.

MeSH terms

  • Animals
  • Astrocytes* / metabolism
  • Astrocytes* / virology
  • Brain / metabolism
  • Brain / virology
  • Cell Line
  • Humans
  • Macaca mulatta*

Grants and funding

We thank Bundesministerium für Bildung und Forschung (BMBF) for funding (031L0155 to SP). Funding (031L0155) as used to pay salary for author SR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.