Development of immortalized rhesus macaque kidney cells supporting infection with a panel of viruses.

Abstract

Non-human primate (NHP)-based model systems faithfully reproduce various viral diseases including Ebola, influenza, AIDS and Zika. However, only a small number of NHP cell lines are available and generation of additional cell lines could help to refine these models. We immortalized rhesus macaque kidney cells by lentiviral transduction with a vector encoding telomerase reverse transcriptase (TERT) and report the generation of three TERT-immortalized cell lines derived from rhesus macaque kidney. Expression of the kidney podocyte marker podoplanin on these cells was demonstrated by flow cytometry. Quantitative real-time PCR (qRT-PCR) was employed to demonstrate induction of MX1 expression upon stimulation with interferon (IFN) or viral infection, suggesting a functional IFN system. Further, the cell lines were susceptible to entry driven by the glycoproteins of vesicular stomatitis virus, influenza A virus, Ebola virus, Nipah virus and Lassa virus as assessed by infection with retroviral pseudotypes. Finally, these cells supported growth of Zika virus and the primate simplexviruses Cercopithecine alphaherpesvirus 2 and Papiine alphaherpesvirus 2. In summary, we developed IFN-responsive rhesus macaque kidney cell lines that allowed entry driven by diverse viral glycoproteins and were permissive to infection with Zika virus and primate simplexviruses. These cell lines will be useful for efforts to analyze viral infections of the kidney in macaque models.