SUMOylation of the human cytomegalovirus 72-kilodalton IE1 protein facilitates expression of the 86-kilodalton IE2 protein and promotes viral replication

Michael Nevels, Wolfram Brune, Thomas Shenk

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

Abstract

The 72-kDa immediate-early 1 protein (IE1-72kDa) of human cytomegalovirus has been previously shown to be posttranslationally modified by covalent conjugation to the ubiquitin-related protein SUMO-1. Using an infectious bacterial artificial chromosome clone of human cytomegalovirus, we constructed a mutant virus (BADpmIE1-K450R) that is deficient for SUMOylation of IE1-72 kDa due to a single amino acid exchange in the SUMO-1 attachment site. Compared to wild-type virus, this mutant grew more slowly and generated a reduced yield in infected human fibroblasts, indicating that SUMO modification is required for the full activity of IE1-72 kDa. The lack of SUMOylation did not affect the intranuclear localization of IE1-72 kDa, including its ability to target to and disrupt PML bodies and to bind to mitotic chromatin. Likewise, SUMOylation-deficient IE1-72 kDa activated several viral promoters as efficiently as the wild-type protein. However, the failure to modify IE1-72 kDa resulted in substantially reduced levels of the IE2 transcript and its 86-kDa protein (IE2-86 kDa). These observations suggest that SUMO modification of IE1-72 kDa contributes to efficient HCMV replication by promoting the accumulation of IE2-86 kDa.
Original languageEnglish
Pages (from-to)7803-12
Number of pages10
JournalJournal of Virology
Volume78
Issue number14
DOIs
Publication statusPublished - Jul 2004

Keywords

  • Cell Line
  • Chromosomes, Artificial, Bacterial
  • Cytomegalovirus
  • Gene Expression Regulation, Viral
  • Humans
  • Immediate-Early Proteins
  • Mutation
  • SUMO-1 Protein
  • Trans-Activators
  • Viral Proteins
  • Virus Replication

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