title: Host-viral effects of chromatin assembly factor 1 interaction with HCMV IE2.
abstract: Chromatin assembly factor 1 (CAF1) consisting of p150, p60 and p48 is known to assemble histones onto newly synthesized DNA and thus maintain the chromatin structure. Here, we show that CAF1 expression was induced in human cytomegalovirus (HCMV)-infected cells, concomitantly with global chromatin decondensation. This apparent conflict was thought to result, in part, from CAF1 mislocalization to compartments of HCMV DNA synthesis through binding of its largest subunit p150 to viral immediate-early protein 2 (IE2). p150 interaction with p60 and IE2 facilitated HCMV DNA synthesis. The IE2Q548R mutation, previously reported to result in impaired HCMV growth with unknown mechanism, disrupted IE2/p150 and IE2/histones association in our study. Moreover, IE2 interaction with histones partly depends on p150, and the HCMV-induced chromatin decondensation was reduced in cells ectopically expressing the p150 mutant defective in IE2 binding. These results not only indicate that CAF1 was hijacked by IE2 to facilitate the replication of the HCMV genome, suggesting chromatin assembly plays an important role in herpesviral DNA synthesis, but also provide a model of the virus-induced chromatin instability through CAF1.
authors: Genomics Research Center, Academia Sinica, Taipei 115.
authors: Sung-Bau
authors: SB
authors: Lee
authors: Chung-Fan
authors: CF
authors: Lee
authors: Derick S-C
authors: DS
authors: Ou
authors: Kalpana
authors: K
authors: Dulal
authors: Liang-Hao
authors: LH
authors: Chang
authors: Chen-Han
authors: CH
authors: Ma
authors: Chien-Fu
authors: CF
authors: Huang
authors: Hua
authors: H
authors: Zhu
authors: Young-Sun
authors: YS
authors: Lin
authors: Li-Jung
authors: LJ
authors: Juan
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D056504:Chromatin Assembly Factor-1 / Q000032:analysis / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D003587:Cytomegalovirus / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000032:analysis / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D002843:Chromatin; D056504:Chromatin Assembly Factor-1; D004279:DNA, Viral; D006657:Histones; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D021122:Protein Subunits; D015534:Trans-Activators