The chromatin remodeling factor SPOC1 acts as a cellular restriction factor against human cytomegalovirus by repressing the major immediate-early promoter.
dc.contributor.author | Reichel, Anna | |
dc.contributor.author | Stilp, Anne-Charlotte | |
dc.contributor.author | Scherer, Myriam | |
dc.contributor.author | Reuter, Nina | |
dc.contributor.author | Lukassen, Sören | |
dc.contributor.author | Kasmapour, Bahram | |
dc.contributor.author | Schreiner, Sabrina | |
dc.contributor.author | Cicin-Sain, Luka | |
dc.contributor.author | Winterpacht, Andreas | |
dc.contributor.author | Stamminger, Thomas | |
dc.date.accessioned | 2018-06-21T13:11:20Z | |
dc.date.available | 2018-06-21T13:11:20Z | |
dc.date.issued | 2018-05-09 | |
dc.identifier.issn | 1098-5514 | |
dc.identifier.pmid | 29743358 | |
dc.identifier.doi | 10.1128/JVI.00342-18 | |
dc.identifier.uri | http://hdl.handle.net/10033/621407 | |
dc.description.abstract | The cellular protein SPOC1 (survival time-associated PHD finger protein in ovarian cancer 1) acts as a regulator of chromatin structure and DNA damage response. It binds H3K4me2/3 containing chromatin and promotes DNA condensation by recruiting corepressors such as KAP-1 and H3K9 methyltransferases. Previous studies identified SPOC1 as a restriction factor against human adenovirus (HAdV) infection that is antagonized by E1B-55K/E4orf6-dependent proteasomal degradation. Here, we demonstrate that, in contrast to HAdV-infected cells, SPOC1 is transiently upregulated during the early phase of HCMV replication. We show that expression of the immediate-early protein 1 (IE1) is sufficient and necessary to induce SPOC1. Additionally, we discovered that during later stages of infection SPOC1 is downregulated in a GSK-3β-dependent manner. We provide evidence that SPOC1 overexpression severely impairs HCMV replication by repressing the initiation of viral immediate early (IE) gene expression. Consistently, we observed that SPOC1-depleted primary human fibroblasts displayed augmented initiation of viral IE gene expression. This occurs in a MOI-dependent manner, a defining hallmark of intrinsic immunity. Interestingly, repression requires the presence of high SPOC1 levels at the start of infection while a later upregulation had no negative impact suggesting distinct temporal roles of SPOC1 during the HCMV replicative cycle. Mechanistically, we observed a highly specific association of SPOC1 with the major immediate-early promoter (MIEP) strongly suggesting that SPOC1 inhibits HCMV replication by MIEP binding and subsequent recruitment of heterochromatin building factors. Thus, our data add SPOC1 as a novel factor to the endowment of a host cell to restrict cytomegalovirus infections. | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/us/ | * |
dc.title | The chromatin remodeling factor SPOC1 acts as a cellular restriction factor against human cytomegalovirus by repressing the major immediate-early promoter. | en_US |
dc.type | Article | en_US |
dc.contributor.department | Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. | en_US |
refterms.dateFOA | 2018-06-21T13:11:21Z | |
dc.source.journaltitle | Journal of virology |