title: The human cytomegalovirus-specific UL1 gene encodes a late-phase glycoprotein incorporated in the virion envelope.
abstract: We have investigated the previously uncharacterized human cytomegalovirus (HCMV) UL1 open reading frame (ORF), a member of the rapidly evolving HCMV RL11 family. UL1 is HCMV specific; the absence of UL1 in chimpanzee cytomegalovirus (CCMV) and sequence analysis studies suggest that UL1 may have originated by the duplication of an ancestor gene from the RL11-TRL cluster (TRL11, TRL12, and TRL13). Sequence similarity searches against human immunoglobulin (Ig)-containing proteins revealed that HCMV pUL1 shows significant similarity to the cellular carcinoembryonic antigen-related (CEA) protein family N-terminal Ig domain, which is responsible for CEA ligand recognition. Northern blot analysis revealed that UL1 is transcribed during the late phase of the viral replication cycle in both fibroblast-adapted and endotheliotropic strains of HCMV. We characterized the protein encoded by hemagglutinin (HA)-tagged UL1 in the AD169-derived HB5 background. UL1 is expressed as a 224-amino-acid type I transmembrane glycoprotein which becomes detectable at 48 h postinfection. In infected human fibroblasts, pUL1 colocalized at the cytoplasmic site of virion assembly and secondary envelopment together with TGN-46, a marker for the trans-Golgi network, and viral structural proteins, including the envelope glycoprotein gB and the tegument phosphoprotein pp28. Furthermore, analyses of highly purified AD169 UL1-HA epitope-tagged virions revealed that pUL1 is a novel constituent of the HCMV envelope. Importantly, the deletion of UL1 in HCMV TB40/E resulted in reduced growth in a cell type-specific manner, suggesting that pUL1 may be implicated in regulating HCMV cell tropism.
authors.affiliation: Immunology Unit, Pompeu Fabra University, Barcelona, Spain.
authors.forename: Medya
authors.initials: M
authors.lastname: Shikhagaie
authors.forename: Eva
authors.initials: E
authors.lastname: Mercé-Maldonado
authors.forename: Elena
authors.initials: E
authors.lastname: Isern
authors.forename: Aura
authors.initials: A
authors.lastname: Muntasell
authors.forename: M Mar
authors.initials: MM
authors.lastname: Albà
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Ana
authors.initials: A
authors.lastname: Angulo
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D023061:Gene Order; D005814:Genes, Viral; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D016415:Sequence Alignment; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014771:Virion / Q000737:chemistry / Q000378:metabolism*; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D006023:Glycoproteins; D014759:Viral Envelope Proteins