Table_1_An iPSC-Derived Myeloid Lineage Model of Herpes Virus Latency and Reactivation.XLSX

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.

单纯疱疹病毒经历终身的潜伏感染，对免疫抑制者而言可能具有致命风险。人类巨细胞病毒（HCMV）的潜伏和再激活模型包括原始髓系细胞，这些细胞被认为是HCMV在体内潜伏携带和再激活的重要因素。然而，原始细胞在获取上受限，且难以培养和进行基因修饰；所有这些因素都阻碍了我们全面理解这种持续的人体病原体与宿主之间的相互作用。我们现采用诱导多能干细胞（iPSCs）构建了一种细胞模型系统，用以研究HCMV在不同髓系细胞分化后的潜伏和再激活。我们的研究结果表明，iPSCs能够有效模拟原始髓系细胞中的HCMV潜伏/溶解转换过程，从而为病毒潜伏/溶解开关的分子研究提供了可能。此模型亦适用于分析其他病毒，如人类免疫缺陷病毒（HIV）和寨卡病毒，这些病毒同样感染髓系细胞。