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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.<\/jats:p>","DOI":"10.1128\/jvi.01955-12","type":"journal-article","created":{"date-parts":[[2012,11,23]],"date-time":"2012-11-23T01:44:21Z","timestamp":1353635061000},"page":"1720-1732","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["The Human Cytomegalovirus UL51 Protein Is Essential for Viral Genome Cleavage-Packaging and Interacts with the Terminase Subunits pUL56 and pUL89"],"prefix":"10.1128","volume":"87","author":[{"given":"Eva Maria","family":"Borst","sequence":"first","affiliation":[{"name":"Institute for Virology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kleine-Albers","sequence":"additional","affiliation":[{"name":"Institute for Virology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildar","family":"Gabaev","sequence":"additional","affiliation":[{"name":"Institute for Virology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Babi\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute for Virology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Binz","sequence":"additional","affiliation":[{"name":"Institute for Virology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Degenhardt","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Leibniz University Hannover, Hannover, Germany, and Helmholtz Centre for Infection Research, Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Kalesse","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Leibniz University Hannover, Hannover, Germany, and Helmholtz Centre for Infection Research, Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stipan","family":"Jonji\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Bauerfeind","sequence":"additional","affiliation":[{"name":"Institute for Cell Biology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Messerle","sequence":"additional","affiliation":[{"name":"Institute for Virology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"2702","volume-title":"Fields virology","author":"Mocarski ES","year":"2007","unstructured":"MocarskiES ShenkT PassRF. 2007. 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