UL84-independent replication of human cytomegalovirus strains conferred by a single codon change in UL122
| Autor: | David J. Spector |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
DNA Replication
Gene Expression Regulation Viral viruses Amino Acid Motifs Molecular Sequence Data Cytomegalovirus Eukaryotic DNA replication Origin of replication Pre-replication complex Virus Replication UL122 variants Immediate-Early Proteins DNA replication factor CDT1 Viral Proteins Transcriptional activation Replication factor C Control of chromosome duplication Virology Humans Amino Acid Sequence Codon Genetics Lytic origin of replication biology UL84-independent replication Human cytomegalovirus Viral DNA replication Licensing factor Cytomegalovirus Infections biology.protein Trans-Activators Origin recognition complex |
| Zdroj: | Virology. 476 |
| ISSN: | 1096-0341 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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