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

Abstract

Non-human primate (NHP)-based model systems are important for biomedical research, due to the close phylogenetic relationship and physiologic similarities of NHP and humans. In infection research, NHP models are used to model 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). Expression of kidney markers on these cells was analyzed by flow cytometry and quantitative real-time PCR (qRT-PCR) was employed to determine functionality of the interferon (IFN) system. Finally, we assessed susceptibility and permissiveness for virus infection by the use of pseudotyped particles and replication-competent viruses. We report the generation of three TERT-immortalized cell lines derived from rhesus macaque kidney. The cell lines expressed the podocyte marker podoplanin and expressed MX1 upon stimulation with IFN or viral infection. 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. Finally, these cells supported growth of Zika virus (ZIKV) and the primate simplexviruses Cercopithecine alphaherpesvirus 2 (CeHV2) and Papiine alphaherpesvirus 2 (PaHV2). 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.