The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89.

2.50
Hdl Handle:
http://hdl.handle.net/10033/291116
Title:
The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89.
Authors:
Borst, Eva Maria; Kleine-Albers, Jennifer; Gabaev, Ildar; Babic, Marina; Wagner, Karen; Binz, Anne; Degenhardt, Inga; Kalesse, Markus; Jonjic, Stipan; Bauerfeind, Rudolf; Messerle, Martin
Abstract:
Cleavage 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.
Affiliation:
Institute for Virology, Hannover Medical School, Hannover, Germany.
Citation:
The 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.
Journal:
Journal of virology
Issue Date:
Feb-2013
URI:
http://hdl.handle.net/10033/291116
DOI:
10.1128/JVI.01955-12
PubMed ID:
23175377
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
publications of the research group immune aging and chronic infections (IMCI)

Full metadata record

DC FieldValue Language
dc.contributor.authorBorst, Eva Mariaen_GB
dc.contributor.authorKleine-Albers, Jenniferen_GB
dc.contributor.authorGabaev, Ildaren_GB
dc.contributor.authorBabic, Marinaen_GB
dc.contributor.authorWagner, Karenen_GB
dc.contributor.authorBinz, Anneen_GB
dc.contributor.authorDegenhardt, Ingaen_GB
dc.contributor.authorKalesse, Markusen_GB
dc.contributor.authorJonjic, Stipanen_GB
dc.contributor.authorBauerfeind, Rudolfen_GB
dc.contributor.authorMesserle, Martinen_GB
dc.date.accessioned2013-05-15T09:40:38Z-
dc.date.available2013-05-15T09:40:38Z-
dc.date.issued2013-02-
dc.identifier.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.en_GB
dc.identifier.issn1098-5514-
dc.identifier.pmid23175377-
dc.identifier.doi10.1128/JVI.01955-12-
dc.identifier.urihttp://hdl.handle.net/10033/291116-
dc.description.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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of virologyen_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshCytomegalovirusen_GB
dc.subject.meshDNA, Viralen_GB
dc.subject.meshEndodeoxyribonucleasesen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHydrolysisen_GB
dc.subject.meshViral Proteinsen_GB
dc.subject.meshViral Structural Proteinsen_GB
dc.subject.meshVirus Assemblyen_GB
dc.titleThe human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89.en
dc.typeArticleen
dc.contributor.departmentInstitute for Virology, Hannover Medical School, Hannover, Germany.en_GB
dc.identifier.journalJournal of virologyen_GB

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