TY - JOUR
T1 - An iPSC-Derived Myeloid Lineage Model of Herpes Virus Latency and Reactivation
AU - Poole, Emma
AU - Huang, Christopher J. Z.
AU - Forbester, Jessica
AU - Shnayder, Miri
AU - Nachshon, Aharon
AU - Kweider, Baraa
AU - Basaj, Anna
AU - Smith, Daniel
AU - Jackson, Sarah Elizabeth
AU - Liu, Bin
AU - Shih, Joy
AU - Kiskin, Fedir N.
AU - Roche, K.
AU - Murphy, E.
AU - Wills, Mark R.
AU - Morrell, Nicholas W.
AU - Dougan, Gordon
AU - Stern-Ginossar, Noam
AU - Rana, Amer A.
AU - Sinclair, John
N1 - The authors would like to thank Linda Teague for technical assistance. This research was supported by the Cambridge NIHR BRC Cell Phenotyping Hub. In particular, the authors wish to thank Esther Perez for her advice and support in cell sorting. Author Contributions BL, EM, KR, MW, SJ, and JSh performed the experiments. EP, CH, AB, JF, MS, AN, DS, NS-G, FK, NM, and BK performed the experiments and analyzed the data. EP, JSi, AR, and GD designed the experiments and analyzed the data. EP, AR, and JSi wrote the manuscript. Funding This work was funded by an MRC Programme grant: RCUK | Medical Research Council (MRC, grant G:0701279), the British Heart Foundation (BHF) project grant (PG/14/31/), the BHF Cambridge Centre of Research Excellence, the Cambridge National Institute for Health Research Biomedical Research Centre (NIHR BRC), and the Dinosaur Trust (project grant DT001).
PY - 2019/10/9
Y1 - 2019/10/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074146331&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fmicb.2019.02233
DO - https://doi.org/10.3389/fmicb.2019.02233
M3 - مقالة
SN - 1664-302X
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 2233
ER -