Host-viral effects of chromatin assembly factor 1 interaction with HCMV IE2

Sung-Bau Lee, Chung-Fan Lee, Derick S C Ou, Kalpana Dulal, Liang-Hao Chang, Chen-Han Ma, Chien-Fu Huang, Hua Zhu, Young-Sun Lin, Li-Jung Juan

Research output: Contribution to journalArticle

7 Citations (Scopus)

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. © 2011 IBCB, SIBS, CAS All rights reserved.
Original languageEnglish
Pages (from-to)1230-1247
Number of pages18
JournalCell Research
Volume21
Issue number8
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • chromatin assembly factor 1
  • chromatin structure
  • human cytomegalovirus
  • immediate-early protein 2
  • histone
  • IE2 protein, Cytomegalovirus
  • immediate early protein
  • transactivator protein
  • virus DNA
  • amino acid substitution
  • article
  • cell line
  • chromatin
  • chromatin assembly and disassembly
  • Cytomegalovirus
  • genetics
  • host pathogen interaction
  • human
  • metabolism
  • protein binding
  • protein subunit
  • virus replication
  • Amino Acid Substitution
  • Cell Line
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Chromatin Assembly Factor-1
  • DNA, Viral
  • Histones
  • Host-Pathogen Interactions
  • Humans
  • Immediate-Early Proteins
  • Protein Binding
  • Protein Subunits
  • Trans-Activators
  • Virus Replication
  • Human herpesvirus 5

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  • Cite this

    Lee, S-B., Lee, C-F., Ou, D. S. C., Dulal, K., Chang, L-H., Ma, C-H., Huang, C-F., Zhu, H., Lin, Y-S., & Juan, L-J. (2011). Host-viral effects of chromatin assembly factor 1 interaction with HCMV IE2. Cell Research, 21(8), 1230-1247. https://doi.org/10.1038/cr.2011.53