Show simple item record

dc.contributor.authorReichel, Anna
dc.contributor.authorStilp, Anne-Charlotte
dc.contributor.authorScherer, Myriam
dc.contributor.authorReuter, Nina
dc.contributor.authorLukassen, Sören
dc.contributor.authorKasmapour, Bahram
dc.contributor.authorSchreiner, Sabrina
dc.contributor.authorCicin-Sain, Luka
dc.contributor.authorWinterpacht, Andreas
dc.contributor.authorStamminger, Thomas
dc.date.accessioned2018-06-21T13:11:20Z
dc.date.available2018-06-21T13:11:20Z
dc.date.issued2018-05-09
dc.identifier.issn1098-5514
dc.identifier.pmid29743358
dc.identifier.doi10.1128/JVI.00342-18
dc.identifier.urihttp://hdl.handle.net/10033/621407
dc.description.abstractThe 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.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.titleThe chromatin remodeling factor SPOC1 acts as a cellular restriction factor against human cytomegalovirus by repressing the major immediate-early promoter.en_US
dc.typeArticleen_US
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en_US
refterms.dateFOA2018-06-21T13:11:21Z
dc.source.journaltitleJournal of virology


Files in this item

Thumbnail
Name:
Reichel et al.pdf
Size:
4.168Mb
Format:
PDF
Description:
accepted manuscript

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-ShareAlike 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States