Data_Sheet_1_An iPSC-Derived Myeloid Lineage Model of Herpes Virus Latency and Reactivation.docx

Herpesviruses undergo life-long latent infection which can be life-threatening in the immunocompromised. Models of latency and reactivation of human cytomegalovirus (HCMV) include primary myeloid cells, cells known to be important for HCMV latent carriage and reactivation in vivo. However, primary cells are limited in availability, and difficult to culture and to genetically modify; all of which have hampered our ability to fully understand virus/host interactions of this persistent human pathogen. We have now used iPSCs to develop a model cell system to study HCMV latency and reactivation in different cell types after their differentiation down the myeloid lineage. Our results show that iPSCs can effectively mimic HCMV latency/reactivation in primary myeloid cells, allowing molecular interrogations of the viral latent/lytic switch. This model may also be suitable for analysis of other viruses, such as HIV and Zika, which also infect cells of the myeloid lineage.

单纯疱疹病毒在免疫受损宿主体内可引起终身潜伏感染，甚至威胁生命。人类巨细胞病毒（HCMV）的潜伏和再激活模型包括原代髓系细胞，这些细胞在HCMV原发潜伏和体内再激活过程中扮演着重要角色。然而，原代细胞在获取、培养以及基因改造方面存在限制，这些因素均阻碍了我们全面理解这种慢性人源病原体与宿主相互作用的进程。本研究中，我们利用诱导多能干细胞（iPSCs）构建了一种细胞模型系统，以研究不同髓系分化阶段细胞中HCMV的潜伏和再激活现象。我们的研究结果表明，iPSCs能够有效地模拟原代髓系细胞中的HCMV潜伏/溶解转换过程，从而为分子水平上的病毒潜伏/溶解转换机制研究提供了可能。此外，该模型也可能适用于分析其他感染髓系细胞的病毒，如HIV和寨卡病毒。