Champion, Anna;
Rowland, Alexandra;
Yee, Levia;
van den Boomen, Dick;
Reeves, Matthew;
Lehner, Paul;
Sinclair, John;
(2023)
MORC3 represses the HCMV major immediate early promoter in myeloid cells in the absence of PML nuclear bodies.
Journal of Medical Virology
, 95
(11)
, Article e29227. 10.1002/jmv.29227.
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Abstract
Human cytomegalovirus (HCMV) can undergo either a latent or a lytic infection in cells of the myeloid lineage. Whilst the molecular mechanisms which determine the outcome of infection are far from clear, it is well established that a key factor is the differential regulation of the major immediate early promoter (MIEP) responsible for driving lytic immediate early gene expression. Using a myelomonocytic cell line stably transduced with a GFP reporter under the control of the MIEP, which recapitulates MIEP regulation in the context of virus infection, we have used an unbiased CRISPR-Cas9 sub-genomic, epigenetic library screen to identify novel cellular factors involved in MIEP repression during establishment and maintenance of latency in myeloid cells. One such cellular factor identified was MORC3. Consistent with MORC3 being a robust repressor of the MIEP, we show that THP1 cells devoid of MORC3 fail to establish latency. We also show that MORC3 is induced during latent infection, recruited to the MIEP and forms MORC3 nuclear bodies (MORC3-NBs) which, interestingly, co-localize with viral genomes. Finally, we show that the latency-associated functions of MORC3 are regulated by the deSUMOylase activity of the viral latency-associated LUNA protein likely to prevent untimely HCMV reactivation.
| Type: | Article |
|---|---|
| Title: | MORC3 represses the HCMV major immediate early promoter in myeloid cells in the absence of PML nuclear bodies |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jmv.29227 |
| Publisher version: | https://onlinelibrary.wiley.com/loi/10969071 |
| Language: | English |
| Additional information: | © 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10181038 |
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