Infection of human induced pluripotent stem cells (hiPSCs) by an oncogenic herpesvirus

As one of major human oncogenic viruses, Kaposi Sarcoma-associated Herpesvirus (KSHV) is closely related to several cancers such as Kaposi sarcoma (KS) and primary effusion lymphoma (PEL). KSHV can infect a broad tropism of human primary cells in vitro and in vivo. Embryonic stem cell-like pluripotent stem cells can be generated by the simultaneous introduction of several factors, into somatic cells, yielding induced pluripotent stem (iPS) cells. In the current study, we report that KSHV successfully establishes latent infection in human induced pluripotent stem cells (hiPSCs), which can be completely induced to lytic reactivation and release infectious virions. KSHV de novo infection arrests the growth of hiPSCs through inducing cell apoptosis. Transcriptomic analysis revealed significant changes in global cellular gene expression in KSHV-infected hiPSCs as well as lytically induced cells. Our findings demonstrate hiPSCs as a powerful tool to explore the potential impacts of KSHV infection on stem cells functions and virus pathogenesis in stem cells differentiated cells.