{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:03:00Z","timestamp":1792803780910,"version":"4.5.0"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["MA1289\/11-1"],"award-info":[{"award-number":["MA1289\/11-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agence Nationale de la Recherche under projects ProFI, Proteomics French Infrastructure","award":["ANR-10-INBS-08"],"award-info":[{"award-number":["ANR-10-INBS-08"]}],"id":[{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"GRAL, a program from the Chemistry Biology Health (CBH), Graduate School of University Grenoble Alpes","award":["ANR-17-EURE-0003"],"award-info":[{"award-number":["ANR-17-EURE-0003"]}],"id":[{"id":"https:\/\/ror.org\/02rx3b187","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The regulation of the nucleocytoplasmic release of herpesviral capsids is defined by the process of nuclear egress. Due to their large size, nuclear capsids are unable to traverse via nuclear pores, so that herpesviruses evolved to develop a vesicular transport pathway mediating their transition through both leaflets of the nuclear membrane. This process involves regulatory proteins, which support the local distortion of the nuclear envelope. For human cytomegalovirus (HCMV), the nuclear egress complex (NEC) is determined by the pUL50-pUL53 core that initiates multicomponent assembly with NEC-associated proteins and capsids. Hereby, pUL50 serves as a multi-interacting determinant that recruits several viral and cellular factors by direct and indirect contacts. Recently, we generated an ORF-UL50-deleted recombinant HCMV in pUL50-complementing cells and obtained first indications of putative additional functions of pUL50. In this study, we produced purified \u0394UL50 particles under both complementing (\u0394UL50C) and non-complementing (\u0394UL50N) conditions and performed a phenotypical characterization. Findings were as follows: (i) \u0394UL50N particle preparations exhibited a clear replicative defect in qPCR-based infection kinetics compared to \u0394UL50C particles; (ii) immuno-EM analysis of \u0394UL50C did not reveal major changes in nuclear distribution of pUL53 and lamin A\/C; (iii) mass spectrometry-based quantitative proteomics showed a large concordance of protein contents in the NIEP fractions of \u0394UL50C and \u0394UL50N particles, but virion fraction was close to the detection limit for \u0394UL50N; (iv) confocal imaging of viral marker proteins of immediate early (IE) and later phases of \u0394UL50N infection indicated a very low number of cells showing an onset of viral lytic protein expression; and, finally (v) quantitative measurements of encapsidated genomes provided evidence for a substantial reduction in the DNA contents in \u0394UL50N compared to \u0394UL50C particles. In summary, the results point to a complex and important regulatory role of the HCMV nuclear egress protein pUL50 in the maturation of infectious virus.<\/jats:p>","DOI":"10.3390\/cells10113119","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:02:41Z","timestamp":1636671761000},"page":"3119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Complex Regulatory Role of Cytomegalovirus Nuclear Egress Protein pUL50 in the Production of Infectious Virus"],"prefix":"10.3390","volume":"10","author":[{"given":"Sigrun","family":"H\u00e4ge","sequence":"first","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"B\u00fcscher","sequence":"additional","affiliation":[{"name":"Institute for Virology and Forschungszentrum f\u00fcr Immuntherapie, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7502-1111","authenticated-orcid":false,"given":"Victoria","family":"Pakulska","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), University Grenoble Alpes, CEA, UMR BioSant\u00e9 U1292, CNRS, CEA, FR2048, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3011-8416","authenticated-orcid":false,"given":"Friedrich","family":"Hahn","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Adrait","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), University Grenoble Alpes, CEA, UMR BioSant\u00e9 U1292, CNRS, CEA, FR2048, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffi","family":"Krauter","sequence":"additional","affiliation":[{"name":"Institute for Virology and Forschungszentrum f\u00fcr Immuntherapie, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Maria","family":"Borst","sequence":"additional","affiliation":[{"name":"Institute of Virology, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Schl\u00f6tzer-Schrehardt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Erlangen, FAU, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-6196","authenticated-orcid":false,"given":"Yohann","family":"Cout\u00e9","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), University Grenoble Alpes, CEA, UMR BioSant\u00e9 U1292, CNRS, CEA, FR2048, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo","family":"Plachter","sequence":"additional","affiliation":[{"name":"Institute for Virology and Forschungszentrum f\u00fcr Immuntherapie, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Marschall","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/path.4437","article-title":"The pathogenesis of human cytomegalovirus","volume":"235","author":"Griffiths","year":"2015","journal-title":"J. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/bs.aivir.2015.10.002","article-title":"Nuclear egress of herpesviruses: The prototypic vesicular nucleocytoplasmic transport","volume":"94","author":"Hellberg","year":"2016","journal-title":"Adv. Virus Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00018-017-2595-9","article-title":"Current knowledge on exosome biogenesis and release","volume":"75","author":"Hessvik","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1016\/j.celrep.2015.11.008","article-title":"Crystal Structure of the herpesvirus nuclear egress complex provides insights into inner nuclear membrane remodeling","volume":"13","author":"Weberruss","year":"2015","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/cmi.12044","article-title":"The way out: What we know and do not know about herpesvirus nuclear egress","volume":"15","author":"Mettenleiter","year":"2013","journal-title":"Cell Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.tcb.2012.07.003","article-title":"Alternative nuclear transport for cellular protein quality control","volume":"22","author":"Rose","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.cell.2012.03.032","article-title":"Nuclear envelope budding enables large ribonucleoprotein particle export during synaptic Wnt signaling","volume":"149","author":"Speese","year":"2012","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1128\/JVI.02426-14","article-title":"Human cytomegalovirus UL97 phosphorylates the viral nuclear egress complex","volume":"89","author":"Sharma","year":"2015","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1099\/jgv.0.000931","article-title":"Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus","volume":"98","author":"Sonntag","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Milbradt, J., Hutterer, C., Bahsi, H., Wagner, S., Sonntag, E., Horn, A.H., Kaufer, B.B., Mori, Y., Sticht, H., and Fossen, T. (2016). The Prolyl isomerase pin1 promotes the herpesvirus-induced phosphorylation-dependent disassembly of the nuclear lamina required for nucleocytoplasmic egress. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005825"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1934","DOI":"10.1002\/rmv.1934","article-title":"The human cytomegalovirus nuclear egress complex unites multiple functions: Recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids","volume":"27","author":"Marschall","year":"2017","journal-title":"Rev. Med. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1074\/mcp.M113.035782","article-title":"Proteomic analysis of the multimeric nuclear egress complex of human cytomegalovirus","volume":"13","author":"Milbradt","year":"2014","journal-title":"Mol. Cell Proteom."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"H\u00e4ge, S., Sonntag, E., Svrlanska, A., Borst, E.M., Stilp, A.C., Horsch, D., M\u00fcller, R., Kropff, B., Milbradt, J., and Stamminger, T. (2021). Phenotypical Characterization of the nuclear egress of recombinant cytomegaloviruses reveals defective replication upon orf-ul50 deletion but not pul50 phosphosite mutation. Viruses, 13.","DOI":"10.3390\/v13020165"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.15252\/embj.201592359","article-title":"Structural basis of membrane budding by the nuclear egress complex of herpesviruses","volume":"34","author":"Bigalke","year":"2015","journal-title":"EMBO J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27452","DOI":"10.1074\/jbc.C115.686527","article-title":"Crystal Structure of the human cytomegalovirus pUL50-pUL53 Core nuclear egress complex provides insight into a unique assembly scaffold for virus-host protein interactions","volume":"290","author":"Walzer","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.15252\/embj.201592651","article-title":"Unexpected features and mechanism of heterodimer formation of a herpesvirus nuclear egress complex","volume":"34","author":"Lye","year":"2015","journal-title":"EMBO J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1074\/jbc.RA119.011546","article-title":"High-resolution crystal structures of two prototypical beta- and gamma-herpesviral nuclear egress complexes unravel the determinants of subfamily specificity","volume":"295","author":"Muller","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Schweininger, J., Kriegel, M., H\u00e4ge, S., Conrad, M., Alkhashrom, S., L\u00f6sing, J., Weiler, S., Tillmanns, J., Egerer-Sieber, C., and Decker, A. (2021). The crystal structure of the varicella zoster Orf24-Orf27 nuclear egress complex spotlights multiple determinants of herpesvirus subfamily specificity. J. Biol. Chem., under revision.","DOI":"10.1101\/2021.08.23.457313"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Marschall, M., H\u00e4ge, S., Conrad, M., Alkhashrom, S., Kicuntod, J., Schweininger, J., Kriegel, M., L\u00f6sing, J., Tillmanns, J., and Neipel, F. (2020). Nuclear Egress complexes of HCMV and Other herpesviruses: Solving the puzzle of sequence coevolution, conserved structures and subfamily-spanning binding properties. Viruses, 12.","DOI":"10.3390\/v12060683"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8307","DOI":"10.1128\/jvi.71.11.8307-8315.1997","article-title":"The null mutant of the U(L)31 gene of herpes simplex virus 1: Construction and phenotype in infected cells","volume":"71","author":"Chang","year":"1997","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1128\/JVI.76.1.364-378.2002","article-title":"The interacting UL31 and UL34 gene products of pseudorabies virus are involved in egress from the host-cell nucleus and represent components of primary enveloped but not mature virions","volume":"76","author":"Fuchs","year":"2002","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.virol.2004.07.030","article-title":"Cell lines that support replication of a novel herpes simplex virus 1 UL31 deletion mutant can properly target UL34 protein to the nuclear rim in the absence of UL31","volume":"329","author":"Liang","year":"2004","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11002","DOI":"10.1073\/pnas.97.20.11002","article-title":"The essential protein encoded by the UL31 gene of herpes simplex virus 1 depends for its stability on the presence of UL34 protein","volume":"97","author":"Ye","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1128\/JVI.74.1.117-129.2000","article-title":"Herpes simplex virus type 1 U(L)34 gene product is required for viral envelopment","volume":"74","author":"Roller","year":"2000","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10063","DOI":"10.1128\/JVI.74.21.10063-10073.2000","article-title":"Primary envelopment of pseudorabies virus at the nuclear membrane requires the UL34 gene product","volume":"74","author":"Klupp","year":"2000","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8285","DOI":"10.1128\/JVI.00741-11","article-title":"Nuclear envelope breakdown can substitute for primary envelopment-mediated nuclear egress of herpesviruses","volume":"85","author":"Klupp","year":"2011","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6512","DOI":"10.1128\/JVI.00068-12","article-title":"Analysis of viral and cellular factors influencing herpesvirus-induced nuclear envelope breakdown","volume":"86","author":"Grimm","year":"2012","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1128\/JVI.79.6.3703-3712.2005","article-title":"BFRF1 of Epstein-Barr virus is essential for efficient primary viral envelopment and egress","volume":"79","author":"Farina","year":"2005","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1128\/JVI.02436-07","article-title":"Deletion of Epstein-Barr virus BFLF2 leads to impaired viral DNA packaging and primary egress as well as to the production of defective viral particles","volume":"82","author":"Granato","year":"2008","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8026","DOI":"10.1128\/JVI.78.15.8026-8035.2004","article-title":"Comprehensive mutational analysis of a herpesvirus gene in the viral genome context reveals a region essential for virus replication","volume":"78","author":"Bubeck","year":"2004","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1128\/JVI.80.1.73-84.2006","article-title":"Functional domains of murine cytomegalovirus nuclear egress protein M53\/p38","volume":"80","author":"Lotzerich","year":"2006","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cout\u00e9, Y., Kraut, A., Zimmermann, C., B\u00fcscher, N., Hesse, A.M., Bruley, C., De Andrea, M., Wangen, C., Hahn, F., and Marschall, M. (2020). Mass spectrometry-based characterization of the virion proteome, phosphoproteome, and associated kinase activity of human cytomegalovirus. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060820"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113909","DOI":"10.1016\/j.jviromet.2020.113909","article-title":"A quantitative nuclear egress assay to investigate the nucleocytoplasmic capsid release of human cytomegalovirus","volume":"283","author":"Horsch","year":"2020","journal-title":"J. Virol. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5423","DOI":"10.1128\/JVI.02585-05","article-title":"Deletion of open reading frame UL26 from the human cytomegalovirus genome results in reduced viral growth, which involves impaired stability of viral particles","volume":"80","author":"Lorz","year":"2006","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1099\/vir.0.026799-0","article-title":"Two isoforms of the protein kinase pUL97 of human cytomegalovirus are differentially regulated in their nuclear translocation","volume":"92","author":"Webel","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1002\/pmic.201200565","article-title":"Proteomic characterization of Pseudomonas aeruginosa PAO1 inner membrane","volume":"13","author":"Casabona","year":"2013","journal-title":"Proteomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1093\/bioinformatics\/btaa118","article-title":"Proline: An efficient and user-friendly software suite for large-scale proteomics","volume":"36","author":"Hesse","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14898","DOI":"10.1021\/acs.analchem.0c00328","article-title":"Beyond Target-decoy competition: Stable validation of peptide and protein identifications in mass spectrometry-based discovery proteomics","volume":"92","author":"Bruley","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/bioinformatics\/btw580","article-title":"DAPAR & ProStaR: Software to perform statistical analyses in quantitative discovery proteomics","volume":"33","author":"Wieczorek","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature10098","article-title":"Global quantification of mammalian gene expression control","volume":"473","author":"Busse","year":"2011","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Milbradt, J., Sonntag, E., Wagner, S., Strojan, H., Wangen, C., Lenac Rovis, T., Lisnic, B., Jonjic, S., Sticht, H., and Britt, W.J. (2018). Human cytomegalovirus nuclear capsids associate with the core nuclear egress complex and the viral protein kinase pUL97. Viruses, 10.","DOI":"10.3390\/v10010035"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13979","DOI":"10.1074\/jbc.M109.063628","article-title":"Novel mode of phosphorylation-triggered reorganization of the nuclear lamina during nuclear egress of human cytomegalovirus","volume":"285","author":"Milbradt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9633","DOI":"10.1128\/JVI.01415-14","article-title":"The tegument protein pp65 of human cytomegalovirus acts as an optional scaffold protein that optimizes protein uploading into viral particles","volume":"88","author":"Reyda","year":"2014","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1080\/15548627.2020.1732686","article-title":"Autophagy interferes with human cytomegalovirus genome replication, morphogenesis, and progeny release","volume":"17","author":"Zimmermann","year":"2021","journal-title":"Autophagy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/0042-6822(83)90122-8","article-title":"Isolation and characterization of a noninfectious virion-like particle released from cells infected with human strains of cytomegalovirus","volume":"130","author":"Irmiere","year":"1983","journal-title":"Virology"},{"key":"ref_46","first-page":"187","article-title":"Structure and formation of the cytomegalovirus virion","volume":"325","author":"Gibson","year":"2008","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_47","unstructured":"Knipe, D.M., and Howley, P.M. (2013). Cytomegaloviruses. Fields Virology, Lippincott Williams & Wilkins. [5th ed.]."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1128\/MMBR.00040-07","article-title":"Tegument proteins of human cytomegalovirus","volume":"72","author":"Kalejta","year":"2008","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1743-422X-9-22","article-title":"Human cytomegalovirus tegument proteins (pp65, pp71, pp150, pp28)","volume":"9","author":"Tomtishen","year":"2012","journal-title":"Virol. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00462","DOI":"10.1128\/JVI.00462-18","article-title":"Transmembrane protein pUL50 of Human cytomegalovirus inhibits ISGylation by downregulating UBE1L","volume":"92","author":"Lee","year":"2018","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e00110","DOI":"10.1128\/JVI.00110-20","article-title":"The human cytomegalovirus transmembrane protein pUL50 induces loss of VCP\/p97 and is regulated by a small isoform of pUL50","volume":"94","author":"Lee","year":"2020","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e00271","DOI":"10.1128\/JVI.00271-17","article-title":"Herpes simplex virus 1 UL34 protein regulates the global architecture of the endoplasmic reticulum in infected cells","volume":"91","author":"Maeda","year":"2017","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.micinf.2020.08.002","article-title":"BFRF1 protein is involved in EBV-mediated autophagy manipulation","volume":"22","author":"Gonnella","year":"2020","journal-title":"Microbes Infect."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.3389\/fimmu.2020.513383","article-title":"Epstein-barr virus early protein BFRF1 suppresses IFN-\u03b2 activity by inhibiting the activation of IRF3","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1096\/fj.201701253R","article-title":"Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy","volume":"32","author":"Liu","year":"2018","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sch\u00fctz, M., Steingruber, M., Socher, E., M\u00fcller, R., Wagner, S., K\u00f6gel, M., Sticht, H., and Marschall, M. (2021). Functional relevance of the interaction between human cyclins and the cytomegalovirus-encoded CDK-like protein kinase pUL97. Viruses, 13.","DOI":"10.3390\/v13071248"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1099\/vir.0.052571-0","article-title":"The cytomegalovirus egress proteins pUL50 and pUL53 are translocated to the nuclear envelope through two distinct modes of nuclear import","volume":"94","author":"Schmeiser","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1128\/JVI.00192-14","article-title":"Differential properties of cytomegalovirus pUL97 kinase isoforms affect viral replication and maribavir susceptibility","volume":"88","author":"Webel","year":"2014","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1128\/AAC.05908-11","article-title":"In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses","volume":"56","author":"Marschall","year":"2012","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:28:21Z","timestamp":1760167701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,11]]},"references-count":59,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cells10113119"],"URL":"https:\/\/doi.org\/10.3390\/cells10113119","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,11]]}}}