iPSCs derived from endothelial progenitors model latency and reactivation during human cytomegalovirus infection

To date, models of human cytomegalovirus (HCMV) latency and reactivation have depended on the use of primary myeloid cells, which have limited availability, are difficult to culture and are challenging to genetically modify. We now show that induced pluripotent stem cells (iPSCs) derived from circulating late outgrowth endothelial progenitors (EPC) can be differentiated down the myeloid lineage, where HCMV latent carriage and reactivation is known to occur in vivo, and act as a model to allow the interrogation of viral and cellular factors involved in latency and reactivation of this persistent human pathogen. In contrast, monocytes generated from iPSCs derived from de-differentiated fibroblasts failed to support HCMV latent carriage. These iPSCs derived from EPCs may also be suitable for in depth genetic interrogation of other viruses which also infect cells of the myeloid lineage, such as HIV and Zika.