title: UL84-independent replication of human cytomegalovirus strains conferred by a single codon change in UL122.
abstract: The UL84 gene of human cytomegalovirus (HCMV) is thought to be involved in the initiation of viral DNA replication, and is essential for replication of strains AD169 and Towne. Hence, discovery that strain TB40-BAC4 is viable in the absence of UL84 presented an enigma requiring an explanation. Data reported here show that strain TR also tolerated loss of UL84, whereas strains FIX, Merlin, Ph, and Toledo did not. UL84-independent growth required the viral replication origin. The genetic locus in TB40 that controls UL84 dependence was mapped to codon 388 of the UL122 gene, which encodes the immediate early 2 (IE2) 86kD protein. Introduction of this TB40-BAC4 variant (H388D) into FIX and Toledo clones converted these strains to UL84 independence. These results provide genetic evidence in virus-infected cells that supports the hypothesis that UL122 participates in the initiation of viral DNA replication by a mechanism involving transcription-mediated activation of the origin.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, The Pennsylvania State University, H107, 500 University Drive, Hershey, PA 17033, USA. Electronic address: dspector@psu.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Spector
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D003062:Codon; D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000821:virology*; D004261:DNA Replication; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D003062:Codon; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014764:Viral Proteins; C072218:UL84 protein, Cytomegalovirus
keywords: Human cytomegalovirus; Lytic origin of replication; Transcriptional activation; UL122 variants; UL84-independent replication; Viral DNA replication