title: Human cytomegalovirus immediate-early gene expression is restricted by the nuclear domain 10 component Sp100.
abstract: Nuclear domains 10 (ND10s) are discrete subnuclear structures that contain the three major protein components promyelocytic leukaemia protein (PML), hDaxx and Sp100. Previous studies identified the ND10-components PML and hDaxx as cellular restriction factors that independently counteract human cytomegalovirus (HCMV) infection via the repression of viral immediate-early (IE) gene expression. Consequently, we asked whether Sp100 is likewise involved in this repressive activity. Infection of Sp100 knockdown (kd) cells with HCMV resulted in a significantly increased plaque-forming ability. In addition, ablation of Sp100 led to a considerable increase in the number of IE1-expressing cells, indicating that Sp100 suppresses the initiation of viral gene expression. Next, double-kd cells, lacking either Sp100/hDaxx or Sp100/PML, were generated. Here, infection resulted in an additional enhancement in HCMV replication efficacy compared with the single-kd cells. Thus, our results further strengthen the concept that the three major ND10-components independently contribute to the cellular restriction of HCMV replication.
authors.affiliation: Institut für Klinische und Molekulare Virologie der Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Adler
authors.affiliation: Institut für Klinische und Molekulare Virologie der Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Tavalai
authors.affiliation: Institut für Klinische und Molekulare Virologie der Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Müller
authors.affiliation: Institut für Klinische und Molekulare Virologie der Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stamminger
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; C094297:CALCOCO2 protein, human; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; C066642:SP100 protein, human