title: The carboxyl-terminal region of human cytomegalovirus IE1491aa contains an acidic domain that plays a regulatory role and a chromatin-tethering domain that is dispensable during viral replication.
abstract: The human cytomegalovirus major immediate-early (alpha) protein IE1(491aa) plays an important role in controlling viral gene expression at low multiplicities of infection. With a transient complementation assay, full-length IE1(491aa) enhanced the growth of ie1 mutant virus CR208 20-fold better than a deletion mutant lacking 71 carboxyl-terminal amino acids (IE1(1-420aa)). A 16-amino-acid domain between amino acids 476 and 491 was both necessary and sufficient for chromatin-tethering activity; however, this domain was completely dispensable for complementation of CR208 replication. The proximal 55-amino-acid acidic domain (amino acids 421 to 475) was found to be most important for function. A deletion mutant lacking only this domain retained chromatin-tethering activity but failed to complement mutant virus. Interestingly, serine phosphorylation (at amino acids 399, 402, 406, 423, 428, 431, 448, 451, and 455) was not required for complementation. These results show that IE1(491aa) is composed of at least two domains that support replication, a region located between amino acids 1 and 399 that complements ie1 mutant virus replication to low levels and an acidic domain between amino acids 421 and 479 that dramatically enhances complementation.
authors.affiliation: Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California 94305-5124, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Reinhardt
authors.forename: Geoffrey B
authors.initials: GB
authors.lastname: Smith
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Himmelheber
authors.forename: Jane
authors.initials: J
authors.lastname: Azizkhan-Clifford
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000821:virology; D015967:Gene Expression Regulation, Viral; D005816:Genetic Complementation Test; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D002843:Chromatin; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D014764:Viral Proteins