The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89.
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AuthorsBorst, Eva Maria
MetadataShow full item record
AbstractCleavage of human cytomegalovirus (HCMV) genomes as well as their packaging into capsids is an enzymatic process mediated by viral proteins and therefore a promising target for antiviral therapy. The HCMV proteins pUL56 and pUL89 form the terminase and play a central role in cleavage-packaging, but several additional viral proteins, including pUL51, had been suggested to contribute to this process, although they remain largely uncharacterized. To study the function of pUL51 in infected cells, we constructed HCMV mutants encoding epitope-tagged versions of pUL51 and used a conditionally replicating virus (HCMV-UL51-ddFKBP), in which pUL51 levels could be regulated by a synthetic ligand. In cells infected with HCMV-UL51-ddFKBP, viral DNA replication was not affected when pUL51 was knocked down. However, no unit-length genomes and no DNA-filled C capsids were found, indicating that cleavage of concatemeric HCMV DNA and genome packaging into capsids did not occur in the absence of pUL51. pUL51 was expressed mainly with late kinetics and was targeted to nuclear replication compartments, where it colocalized with pUL56 and pUL89. Upon pUL51 knockdown, pUL56 and pUL89 were no longer detectable in replication compartments, suggesting that pUL51 is needed for their correct subnuclear localization. Moreover, pUL51 was found in a complex with the terminase subunits pUL56 and pUL89. Our data provide evidence that pUL51 is crucial for HCMV genome cleavage-packaging and may represent a third component of the viral terminase complex. Interference with the interactions between the terminase subunits by antiviral drugs could be a strategy to disrupt the HCMV replication cycle.
CitationThe human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89. 2013, 87 (3):1720-32 J. Virol.
AffiliationInstitute for Virology, Hannover Medical School, Hannover, Germany.
JournalJournal of virology
The following license files are associated with this item:
- Mutual Interplay between the Human Cytomegalovirus Terminase Subunits pUL51, pUL56, and pUL89 Promotes Terminase Complex Formation.
- Authors: Neuber S, Wagner K, Goldner T, Lischka P, Steinbrueck L, Messerle M, Borst EM
- Issue date: 2017 Jun 15
- The C-terminal part of the human cytomegalovirus terminase subunit pUL51 is central for terminase complex assembly.
- Authors: Neuber S, Wagner K, Messerle M, Borst EM
- Issue date: 2018 Jan
- Identification of a short sequence in the HCMV terminase pUL56 essential for interaction with pUL89 subunit.
- Authors: Ligat G, Jacquet C, Chou S, Couvreux A, Alain S, Hantz S
- Issue date: 2017 Aug 18
- First clinical description of letermovir resistance mutation in cytomegalovirus UL51 gene and potential impact on the terminase complex structure.
- Authors: Muller C, Tilloy V, Frobert E, Feghoul L, Garrigue I, Lepiller Q, Mirand A, Sidorov E, Hantz S, Alain S
- Issue date: 2022 Aug
- Targeting the terminase: An important step forward in the treatment and prophylaxis of human cytomegalovirus infections.
- Authors: Gentry BG, Bogner E, Drach JC
- Issue date: 2019 Jan