{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:45:30Z","timestamp":1793072730407,"version":"4.5.0"},"reference-count":119,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99AI151891"],"award-info":[{"award-number":["K99AI151891"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32GM126760"],"award-info":[{"award-number":["F32GM126760"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K12GM133314"],"award-info":[{"award-number":["K12GM133314"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI164698"],"award-info":[{"award-number":["R01AI164698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI147625"],"award-info":[{"award-number":["R01AI147625"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI160821"],"award-info":[{"award-number":["R21AI160821"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI145272"],"award-info":[{"award-number":["R21AI145272"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF2128247"],"award-info":[{"award-number":["NSF2128247"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["55108533"],"award-info":[{"award-number":["55108533"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000875","name":"Pew Charitable Trusts","doi-asserted-by":"publisher","award":["34472"],"award-info":[{"award-number":["34472"]}],"id":[{"id":"10.13039\/100000875","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human herpesviruses, classified into three subfamilies, are double-stranded DNA viruses that establish lifelong latent infections within most of the world\u2019s population and can cause severe disease, especially in immunocompromised people. There is no cure, and current preventative and therapeutic options are limited. Therefore, understanding the biology of these viruses is essential for finding new ways to stop them. Capsids play a central role in herpesvirus biology. They are sophisticated vehicles that shelter the pressurized double-stranded-DNA genomes while ensuring their delivery to defined cellular destinations on the way in and out of the host cell. Moreover, the importance of capsids for multiple key steps in the replication cycle makes their assembly an attractive therapeutic target. Recent cryo-electron microscopy reconstructions of capsids from all three subfamilies of human herpesviruses revealed not only conserved features but also remarkable structural differences. Furthermore, capsid assembly studies have suggested subfamily-specific roles of viral capsid protein homologs. In this review, we compare capsid structures, assembly mechanisms, and capsid protein functions across human herpesvirus subfamilies, highlighting the differences.<\/jats:p>","DOI":"10.3390\/v13101913","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T23:08:31Z","timestamp":1632784111000},"page":"1913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Ins and Outs of Herpesviral Capsids: Divergent Structures and Assembly Mechanisms across the Three Subfamilies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-4774","authenticated-orcid":false,"given":"Elizabeth B.","family":"Draganova","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Valentin","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3113-6958","authenticated-orcid":false,"given":"Ekaterina E.","family":"Heldwein","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-53168-7_1","article-title":"Initial Contact: The First Steps in Herpesvirus Entry","volume":"Volume 223","author":"Osteirrieder","year":"2017","journal-title":"Adv. Anat. Embryol. Cell. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Weidner-Glunde, M., Kruminis-Kaszkiel, E., and Savanagouder, M. (2020). Herpesviral Latency-Common Themes. Pathogens, 9.","DOI":"10.3390\/pathogens9020125"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.jmb.2015.10.001","article-title":"Breaching the Barrier-the Nuclear Envelope in Virus Infection","volume":"428","author":"Mettenleiter","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-3-319-53168-7_7","article-title":"Herpesvirus Nuclear Egress","volume":"Volume 223","author":"Osteirrieder","year":"2017","journal-title":"Advances in Anatomy, Embryology and Cell Biology"},{"key":"ref_5","first-page":"125","article-title":"Nuclear Egress","volume":"41","author":"Draganova","year":"2020","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/978-3-319-53168-7_6","article-title":"Herpesvirus Capsid Assembly and DNA Packaging","volume":"223","author":"Heming","year":"2017","journal-title":"Adv. Anat. Embryol. Cell. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.coviro.2011.06.003","article-title":"Herpesvirus Capsid Assembly: Insights from Structural Analysis","volume":"1","author":"Brown","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1038\/s41564-020-0785-y","article-title":"Near-Atomic Cryo-Electron Microscopy Structures of Varicella-Zoster Virus Capsids","volume":"5","author":"Wang","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/s41564-020-0758-1","article-title":"Structures of Capsid and Capsid-Associated Tegument Complex inside the Epstein-Barr Virus","volume":"5","author":"Liu","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.cell.2019.07.035","article-title":"DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus Kshv","volume":"178","author":"Gong","year":"2019","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5346","DOI":"10.1038\/s41467-019-13064-x","article-title":"Atomic Structure of the Human Herpesvirus 6b Capsid and Capsid-Associated Tegument Complexes","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dai, X., and Zhou, Z.H. (2018). Structure of the Herpes Simplex Virus 1 Capsid with Associated Tegument Protein Complexes. Science, 360.","DOI":"10.1126\/science.aao7298"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yu, X., Jih, J., Jiang, J., and Zhou, Z.H. (2017). Atomic Structure of the Human Cytomegalovirus Capsid with Its Securing Tegument Layer of Pp150. Science, 356.","DOI":"10.1126\/science.aam6892"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1038\/s41467-018-06078-4","article-title":"Structure of the Herpes Simplex Virus Type 2 C-Capsid with Capsid-Vertex-Specific Component","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/s41422-020-0363-0","article-title":"Cryoem Structure of the Tegumented Capsid of Epstein-Barr Virus","volume":"30","author":"Li","year":"2020","journal-title":"Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1038\/s41467-021-24820-3","article-title":"Structural Basis for Genome Packaging, Retention, and Ejection in Human Cytomegalovirus","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Muller, C., Alain, S., Baumert, T.F., Ligat, G., and Hantz, S. (2021). Structures and Divergent Mechanisms in Capsid Maturation and Stabilization Following Genome Packaging of Human Cytomegalovirus and Herpesviruses. Life, 11.","DOI":"10.3390\/life11020150"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1128\/jvi.69.6.3690-3703.1995","article-title":"Assembly of the Herpes Simplex Virus Capsid: Requirement for the Carboxyl-Terminal Twenty-Five Amino Acids of the Proteins Encoded by the Ul26 and Ul26.5 Genes","volume":"69","author":"Thomsen","year":"1995","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1128\/jvi.68.4.2442-2457.1994","article-title":"Assembly of Herpes Simplex Virus (Hsv) Intermediate Capsids in Insect Cells Infected with Recombinant Baculoviruses Expressing Hsv Capsid Proteins","volume":"68","author":"Thomsen","year":"1994","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1099\/0022-1317-75-5-1101","article-title":"Assembly of Herpes Simplex Virus Type 1 Capsids Using a Panel of Recombinant Baculoviruses","volume":"75","author":"Tatman","year":"1994","journal-title":"J. Gen. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1128\/JVI.01733-08","article-title":"Self-Assembly of Epstein-Barr Virus Capsids","volume":"83","author":"Henson","year":"2009","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7201","DOI":"10.1128\/JVI.00423-08","article-title":"Small Capsid Protein Porf65 Is Essential for Assembly of Kaposi\u2019s Sarcoma-Associated Herpesvirus Capsids","volume":"82","author":"Perkins","year":"2008","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6059","DOI":"10.1128\/jvi.68.9.6059-6063.1994","article-title":"Cell-Free Assembly of the Herpes Simplex Virus Capsid","volume":"68","author":"Newcomb","year":"1994","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1006\/jmbi.1996.0587","article-title":"Assembly of the Herpes Simplex Virus Capsid: Characterization of Intermediates Observed During Cell-Free Capsid Formation","volume":"263","author":"Newcomb","year":"1996","journal-title":"J. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4239","DOI":"10.1128\/JVI.73.5.4239-4250.1999","article-title":"Assembly of the Herpes Simplex Virus Procapsid from Purified Components and Identification of Small Complexes Containing the Major Capsid and Scaffolding Proteins","volume":"73","author":"Newcomb","year":"1999","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10540","DOI":"10.1128\/JVI.79.16.10540-10546.2005","article-title":"Involvement of the Portal at an Early Step in Herpes Simplex Virus Capsid Assembly","volume":"79","author":"Newcomb","year":"2005","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Aksyuk, A.A., Newcomb, W.W., Cheng, N., Winkler, D.C., Fontana, J., Heymann, J.B., and Steven, A.C. (2015). Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid. mBio, 6.","DOI":"10.1128\/mBio.01525-15"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s13238-020-00710-0","article-title":"Architecture of the Herpesvirus Genome-Packaging Complex and Implications for DNA Translocation","volume":"11","author":"Yang","year":"2020","journal-title":"Protein Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/(SICI)1099-1654(199707)7:2<107::AID-RMV191>3.0.CO;2-M","article-title":"Capsid Assembly and DNA Packaging in Herpes Simplex Virus","volume":"7","author":"Homa","year":"1997","journal-title":"Rev. Med. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1128\/JVI.74.4.1663-1673.2000","article-title":"Isolation of Herpes Simplex Virus Procapsids from Cells Infected with a Protease-Deficient Mutant Virus","volume":"74","author":"Newcomb","year":"2000","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nsb922","article-title":"Dynamics of Herpes Simplex Virus Capsid Maturation Visualized by Time-Lapse Cryo-Electron Microscopy","volume":"10","author":"Heymann","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1128\/JVI.75.2.687-698.2001","article-title":"Herpes Simplex Virus DNA Cleavage and Packaging Proteins Associate with the Procapsid Prior to Its Maturation","volume":"75","author":"Sheaffer","year":"2001","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ruhge, L.L., Huet, A.G.E., Conway, J.F., and Smith, G.A. (2018). The Apical Region of the Herpes Simplex Virus Major Capsid Protein Promotes Capsid Maturation. J. Virol., 92.","DOI":"10.1128\/JVI.00821-18"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/femsre\/fuy004","article-title":"The Human Cytomegalovirus Terminase Complex as an Antiviral Target: A Close-up View","volume":"42","author":"Ligat","year":"2018","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7428","DOI":"10.1128\/JVI.72.9.7428-7439.1998","article-title":"Herpes Simplex Virus Type 1 Cleavage and Packaging Proteins Ul15 and Ul28 Are Associated with B but Not C Capsids During Packaging","volume":"72","author":"Yu","year":"1998","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1006\/viro.1998.9475","article-title":"Herpes Simplex Virus 1 DNA Cleavage\/Packaging: The Ul28 Gene Encodes a Minor Component of B Capsids","volume":"252","author":"Taus","year":"1998","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1128\/JVI.78.3.1367-1374.2004","article-title":"Quantification of the DNA Cleavage and Packaging Proteins U(L)15 and U(L)28 in a and B Capsids of Herpes Simplex Virus Type 1","volume":"78","author":"Beard","year":"2004","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/nrmicro2559","article-title":"Herpesviruses Remodel Host Membranes for Virus Egress","volume":"9","author":"Johnson","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1128\/jvi.67.3.1357-1364.1993","article-title":"Mutations in Herpes Simplex Virus Type 1 Genes Encoding Vp5 and Vp23 Abrogate Capsid Formation and Cleavage of Replicated DNA","volume":"67","author":"Desai","year":"1993","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1006\/viro.1997.9005","article-title":"Capsids Are Formed in a Mutant Virus Blocked at the Maturation Site of the Ul26 and Ul26.5 Open Reading Frames of Herpes Simplex Virus Type 1 but Are Not Formed in a Null Mutant of Ul38 (Vp19c)","volume":"242","author":"Person","year":"1998","journal-title":"Virology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14223","DOI":"10.1073\/pnas.2334032100","article-title":"Functional Profiling of a Human Cytomegalovirus Genome","volume":"100","author":"Dunn","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1006\/viro.1998.9230","article-title":"Herpes Simplex Virus Type 1 Vp26 Is Not Essential for Replication in Cell Culture but Influences Production of Infectious Virus in the Nervous System of Infected Mice","volume":"247","author":"Desai","year":"1998","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dai, X., Yu, X., Gong, H., Jiang, X., Abenes, G., Liu, H., Shivakoti, S., Britt, W.J., Zhu, H., and Liu, F. (2013). The Smallest Capsid Protein Mediates Binding of the Essential Tegument Protein Pp150 to Stabilize DNA-Containing Capsids in Human Cytomegalovirus. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003525"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E649","DOI":"10.1073\/pnas.1420317112","article-title":"Cryoem and Mutagenesis Reveal That the Smallest Capsid Protein Cements and Stabilizes Kaposi\u2019s Sarcoma-Associated Herpesvirus Capsid","volume":"112","author":"Dai","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.virol.2010.08.017","article-title":"Functional Characterization of Kaposi\u2019s Sarcoma-Associated Herpesvirus Small Capsid Protein by Bacterial Artificial Chromosome-Based Mutagenesis","volume":"407","author":"Sathish","year":"2010","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6838","DOI":"10.1128\/JVI.74.15.6838-6848.2000","article-title":"Evidence for Controlled Incorporation of Herpes Simplex Virus Type 1 Ul26 Protease into Capsids","volume":"74","author":"Sheaffer","year":"2000","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1128\/JVI.01903-06","article-title":"The Amino-Conserved Domain of Human Cytomegalovirus Ul80a Proteins Is Required for Key Interactions During Early Stages of Capsid Formation and Virus Production","volume":"81","author":"Loveland","year":"2007","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1128\/jvi.68.6.3702-3712.1994","article-title":"The Protease of Herpes Simplex Virus Type 1 Is Essential for Functional Capsid Formation and Viral Growth","volume":"68","author":"Gao","year":"1994","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7103","DOI":"10.1073\/pnas.0408826102","article-title":"Dissecting Human Cytomegalovirus Gene Function and Capsid Maturation by Ribozyme Targeting and Electron Cryomicroscopy","volume":"102","author":"Yu","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.virol.2021.02.009","article-title":"Kaposi\u2019s Sarcoma-Associated Herpesvirus Orf17 Plays a Key Role in Capsid Maturation","volume":"558","author":"Tsurumi","year":"2021","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5365","DOI":"10.1128\/jvi.68.9.5365-5374.1994","article-title":"The Size and Symmetry of B Capsids of Herpes Simplex Virus Type 1 Are Determined by the Gene Products of the Ul26 Open Reading Frame","volume":"68","author":"Desai","year":"1994","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1006\/viro.1996.0098","article-title":"Isolation and Characterization of Herpes Simplex Virus Type 1 Mutants Defective in the Ul6 Gene","volume":"217","author":"Patel","year":"1996","journal-title":"Virology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6778","DOI":"10.1128\/JVI.00473-08","article-title":"Amino Acids 143 to 150 of the Herpes Simplex Virus Type 1 Scaffold Protein Are Required for the Formation of Portal-Containing Capsids","volume":"82","author":"Huffman","year":"2008","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5021","DOI":"10.1128\/JVI.00150-08","article-title":"Domain within Herpes Simplex Virus 1 Scaffold Proteins Required for Interaction with Portal Protein in Infected Cells and Incorporation of the Portal Vertex into Capsids","volume":"82","author":"Yang","year":"2008","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10231","DOI":"10.1128\/JVI.01890-07","article-title":"Functions of Varicella-Zoster Virus Orf23 Capsid Protein in Viral Replication and the Pathogenesis of Skin Infection","volume":"82","author":"Chaudhuri","year":"2008","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0022-2836(96)80018-0","article-title":"The Herpes Simplex Virus Procapsid: Structure, Conformational Changes Upon Maturation, and Roles of the Triplex Proteins Vp19c and Vp23 in Assembly","volume":"263","author":"Trus","year":"1996","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9862","DOI":"10.1128\/JVI.77.18.9862-9871.2003","article-title":"Assembly of the Herpes Simplex Virus Capsid: Identification of Soluble Scaffold-Portal Complexes and Their Role in Formation of Portal-Containing Capsids","volume":"77","author":"Newcomb","year":"2003","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1128\/JVI.79.1.132-139.2005","article-title":"Identification of a Region in the Herpes Simplex Virus Scaffolding Protein Required for Interaction with the Portal","volume":"79","author":"Singer","year":"2005","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9396","DOI":"10.1128\/JVI.00986-07","article-title":"Structural Features of the Scaffold Interaction Domain at the N Terminus of the Major Capsid Protein (Vp5) of Herpes Simplex Virus Type 1","volume":"81","author":"Huang","year":"2007","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1128\/jvi.45.3.1056-1064.1983","article-title":"Identification and Characterization of a Herpes Simplex Virus Gene Product Required for Encapsidation of Virus DNA","volume":"45","author":"Preston","year":"1983","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kobayashi, R., Kato, A., Sagara, H., Watanabe, M., Maruzuru, Y., Koyanagi, N., Arii, J., and Kawaguchi, Y. (2017). Herpes Simplex Virus 1 Small Capsomere-Interacting Protein Vp26 Regulates Nucleocapsid Maturation. J. Virol., 91.","DOI":"10.1128\/JVI.01068-17"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"11863","DOI":"10.1128\/JVI.75.23.11863-11867.2001","article-title":"The Pattern of Tegument-Capsid Interaction in the Herpes Simplex Virus Type 1 Virion Is Not Influenced by the Small Hexon-Associated Protein Vp26","volume":"75","author":"Chen","year":"2001","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5832","DOI":"10.1073\/pnas.0500803102","article-title":"Targeting of Herpesvirus Capsid Transport in Axons Is Coupled to Association with Specific Sets of Tegument Proteins","volume":"102","author":"Luxton","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.virusres.2017.04.016","article-title":"Incorporation of the Kaposi\u2019s Sarcoma-Associated Herpesvirus Capsid Vertex-Specific Component (Cvsc) into Self-Assembled Capsids","volume":"236","author":"Grzesik","year":"2017","journal-title":"Virus Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1128\/JVI.75.3.1450-1458.2001","article-title":"Genetic Evidence of an Essential Role for Cytomegalovirus Small Capsid Protein in Viral Growth","volume":"75","author":"Borst","year":"2001","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1099\/0022-1317-65-12-2077","article-title":"Herpes Simplex and \u2018the Herpes Complex\u2019: Diverse Observations and a Unifying Hypothesis. The Eighth Fleming Lecture","volume":"65","author":"Honess","year":"1984","journal-title":"J. Gen. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9096","DOI":"10.1093\/nar\/gku634","article-title":"Major Capsid Reinforcement by a Minor Protein in Herpesviruses and Phage","volume":"42","author":"Liu","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.molcel.2007.04.010","article-title":"Allosteric Signaling and a Nuclear Exit Strategy: Binding of Ul25\/Ul17 Heterodimers to DNA-Filled Hsv-1 Capsids","volume":"26","author":"Trus","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7513","DOI":"10.1128\/JVI.00837-11","article-title":"The Herpes Simplex Virus 1 Ul17 Protein Is the Second Constituent of the Capsid Vertex-Specific Component Required for DNA Packaging and Retention","volume":"85","author":"Toropova","year":"2011","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"12694","DOI":"10.1128\/JVI.01509-14","article-title":"Organization of Capsid-Associated Tegument Components in Kaposi\u2019s Sarcoma-Associated Herpesvirus","volume":"88","author":"Dai","year":"2014","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1016\/j.jmb.2013.06.034","article-title":"Structure of the Pseudorabies Virus Capsid: Comparison with Herpes Simplex Virus Type 1 and Differential Binding of Essential Minor Proteins","volume":"425","author":"Homa","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liu, W., Dai, X., Jih, J., Chan, K., Trang, P., Yu, X., Balogun, R., Mei, Y., Liu, F., and Zhou, Z.H. (2019). Atomic Structures and Deletion Mutant Reveal Different Capsid-Binding Patterns and Functional Significance of Tegument Protein Pp150 in Murine and Human Cytomegaloviruses with Implications for Therapeutic Development. PLoS Pathog., 15.","DOI":"10.2210\/pdb6nhj\/pdbx"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41586-019-1248-6","article-title":"Cryo-Em Structures of Herpes Simplex Virus Type 1 Portal Vertex and Packaged Genome","volume":"570","author":"Liu","year":"2019","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"McElwee, M., Vijayakrishnan, S., Rixon, F., and Bhella, D. (2018). Structure of the Herpes Simplex Virus Portal-Vertex. PLoS Biol., 16.","DOI":"10.1101\/290544"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s13238-020-00711-z","article-title":"Structures of the Portal Vertex Reveal Essential Protein-Protein Interactions for Herpesvirus Assembly and Maturation","volume":"11","author":"Wang","year":"2020","journal-title":"Protein Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.virol.2014.02.023","article-title":"Varicella-Zoster Virus Induces the Formation of Dynamic Nuclear Capsid Aggregates","volume":"454\u2013455","author":"Lebrun","year":"2014","journal-title":"Virology"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Parvate, A.D., Vago, F., Hasan, S.S., Lee, J., Williams, E.P., Lanman, J., and Jonsson, C.B. (2020). A New Inactivation Method to Facilitate Cryo-Em of Enveloped, Rna Viruses Requiring High Containment: A Case Study Using Venezuelan Equine Encephalitis Virus (Veev). J. Virol. Methods, 277.","DOI":"10.1016\/j.jviromet.2019.113792"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"Ucsf Chimera\u2014A Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1128\/JVI.72.5.3779-3788.1998","article-title":"The Herpes Simplex Virus Type 1 U(L)17 Gene Encodes Virion Tegument Proteins That Are Required for Cleavage and Packaging of Viral DNA","volume":"72","author":"Salmon","year":"1998","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1128\/JVI.01889-08","article-title":"Role of the Ul25 Protein in Herpes Simplex Virus DNA Encapsidation","volume":"83","author":"Cockrell","year":"2009","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10755","DOI":"10.1128\/JVI.75.22.10755-10765.2001","article-title":"Packaging of Genomic and Amplicon DNA by the Herpes Simplex Virus Type 1 Ul25-Null Mutant Kul25ns","volume":"75","author":"Stow","year":"2001","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5725","DOI":"10.1128\/JVI.02441-07","article-title":"Partial Functional Complementation of a Pseudorabies Virus Ul25 Deletion Mutant by Herpes Simplex Virus Type 1 Pul25 Indicates Overlapping Functions of Alphaherpesvirus Pul25 Proteins","volume":"82","author":"Kuhn","year":"2008","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6235","DOI":"10.1128\/JVI.02662-05","article-title":"The Capsid-Associated Ul25 Protein of the Alphaherpesvirus Pseudorabies Virus Is Nonessential for Cleavage and Encapsidation of Genomic DNA but Is Required for Nuclear Egress of Capsids","volume":"80","author":"Klupp","year":"2006","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1128\/JVI.72.2.1060-1070.1998","article-title":"The Product of the Herpes Simplex Virus Type 1 Ul25 Gene Is Required for Encapsidation but Not for Cleavage of Replicated Viral DNA","volume":"72","author":"McNab","year":"1998","journal-title":"J. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Brandariz-Nu\u00f1ez, A., Liu, T., Du, T., and Evilevitch, A. (2019). Pressure-Driven Release of Viral Genome into a Host Nucleus Is a Mechanism Leading to Herpes Infection. Elife, 8.","DOI":"10.7554\/eLife.47212"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Snijder, J., Radtke, K., Anderson, F., Scholtes, L., Corradini, E., Baines, J., Heck, A.J.R., Wuite, G.J.L., Sodeik, B., and Roos, W.H. (2017). Vertex-Specific Proteins Pul17 and Pul25 Mechanically Reinforce Herpes Simplex Virus Capsids. J. Virol., 91.","DOI":"10.1128\/JVI.00123-17"},{"key":"ref_88","unstructured":"DeLano, W.L. (2015). The Pymol Molecular Graphics System, Version 2.5.1, Schr\u00f6dinger Inc.. Available online: https:\/\/pymol.org\/2\/support.html."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4058","DOI":"10.1128\/JVI.00012-12","article-title":"The Ul36 Tegument Protein of Herpes Simplex Virus 1 Has a Composite Binding Site at the Capsid Vertices","volume":"86","author":"Cardone","year":"2012","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5084","DOI":"10.3390\/v7092861","article-title":"Tegument Assembly and Secondary Envelopment of Alphaherpesviruses","volume":"7","author":"Owen","year":"2015","journal-title":"Viruses"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1128\/JVI.80.1.201-209.2006","article-title":"The Pseudorabies Virus Vp1\/2 Tegument Protein Is Required for Intracellular Capsid Transport","volume":"80","author":"Luxton","year":"2006","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/cmi.12075","article-title":"Cytosolic Herpes Simplex Virus Capsids Not Only Require Binding Inner Tegument Protein Pul36 but Also Pul37 for Active Transport Prior to Secondary Envelopment","volume":"15","author":"Schipke","year":"2013","journal-title":"Cell Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1128\/JVI.01139-08","article-title":"Herpes Simplex Virus Replication: Roles of Viral Proteins and Nucleoporins in Capsid-Nucleus Attachment","volume":"83","author":"Copeland","year":"2009","journal-title":"J. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1128\/JVI.01895-10","article-title":"A Single Mutation Responsible for Temperature-Sensitive Entry and Assembly Defects in the Vp1-2 Protein of Herpes Simplex Virus","volume":"85","author":"Abaitua","year":"2011","journal-title":"J. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6610","DOI":"10.1128\/JVI.02655-08","article-title":"Herpesvirus Capsid Association with the Nuclear Pore Complex and Viral DNA Release Involve the Nucleoporin Can\/Nup214 and the Capsid Protein Pul25","volume":"83","author":"Pasdeloup","year":"2009","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Huffman, J.B., Daniel, G.R., Falck-Pedersen, E., Huet, A., Smith, G.A., Conway, J.F., and Homa, F.L. (2017). The C Terminus of the Herpes Simplex Virus Ul25 Protein Is Required for Release of Viral Genomes from Capsids Bound to Nuclear Pores. J. Virol., 91.","DOI":"10.1128\/JVI.00641-17"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1128\/JVI.00857-16","article-title":"Herpes Simplex Virus Capsid Localization to Escrt-Vps4 Complexes in the Presence and Absence of the Large Tegument Protein Ul36p","volume":"90","author":"Kharkwal","year":"2016","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e01290-19","DOI":"10.1128\/JVI.01290-19","article-title":"Identification of the Capsid Binding Site in the Herpes Simplex Virus 1 Nuclear Egress Complex and Its Role in Viral Primary Envelopment and Replication","volume":"93","author":"Takeshima","year":"2019","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Draganova, E.B., Zhang, J., Zhou, Z.H., and Heldwein, E.E. (2020). Structural Basis for Capsid Recruitment and Coat Formation During Hsv-1 Nuclear Egress. Elife, 9.","DOI":"10.7554\/eLife.56627"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Selariu, A., Warden, C., Huang, G., Huang, Y., Zaccheus, O., Cheng, T., Xia, N., and Zhu, H. (2010). Genome-Wide Mutagenesis Reveals That Orf7 Is a Novel Vzv Skin-Tropic Factor. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000971"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Aneja, K.K., and Yuan, Y. (2017). Reactivation and Lytic Replication of Kaposi\u2019s Sarcoma-Associated Herpesvirus: An Update. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00613"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"D\u00fcnn-Kittenplon, D., Ashkenazy-Titelman, A., Kalt, I., Lellouche, J.P., Shav-Tal, Y., and Sarid, R. (2021). The Portal Vertex of Kshv Promotes Docking of Capsids at the Nuclear Pores. Viruses, 13.","DOI":"10.3390\/v13040597"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1099\/vir.0.79888-0","article-title":"Genetic Content of Wild-Type Human Cytomegalovirus","volume":"85","author":"Dolan","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"8040","DOI":"10.1128\/JVI.73.10.8040-8052.1999","article-title":"Human Herpesvirus 6b Genome Sequence: Coding Content and Comparison with Human Herpesvirus 6a","volume":"73","author":"Dominguez","year":"1999","journal-title":"J. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1099\/0022-1317-69-7-1531","article-title":"The Complete DNA Sequence of the Long Unique Region in the Genome of Herpes Simplex Virus Type 1","volume":"69","author":"McGeoch","year":"1988","journal-title":"J. Gen. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5975","DOI":"10.1128\/jvi.70.9.5975-5989.1996","article-title":"Determination and Analysis of the Complete Nucleotide Sequence of Human Herpesvirus","volume":"70","author":"Nicholas","year":"1996","journal-title":"J. Virol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1006\/jmbi.1999.3344","article-title":"Cryomicroscopy of Human Cytomegalovirus Virions Reveals More Densely Packed Genomic DNA Than in Herpes Simplex Virus Type 1","volume":"295","author":"Bhella","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7129","DOI":"10.1128\/JVI.02549-10","article-title":"Cytomegalovirus Pul96 Is Critical for the Stability of Pp150-Associated Nucleocapsids","volume":"85","author":"Tandon","year":"2011","journal-title":"J. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1128\/JVI.01776-09","article-title":"Bicaudal D1-Dependent Trafficking of Human Cytomegalovirus Tegument Protein Pp150 in Virus-Infected Cells","volume":"84","author":"Indran","year":"2010","journal-title":"J. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8199","DOI":"10.1128\/JVI.00457-06","article-title":"Betaherpesvirus-Conserved Cytomegalovirus Tegument Protein Ppul32 (Pp150) Controls Cytoplasmic Events During Virion Maturation","volume":"80","author":"AuCoin","year":"2006","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"17510","DOI":"10.1073\/pnas.1312235110","article-title":"Human Cytomegalovirus Tegument Protein Pp150 Acts as a Cyclin A2-Cdk-Dependent Sensor of the Host Cell Cycle and Differentiation State","volume":"110","author":"Bogdanow","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5860","DOI":"10.1128\/JVI.00384-16","article-title":"The Essential Human Cytomegalovirus Proteins Pul77 and Pul93 Are Structural Components Necessary for Viral Genome Encapsidation","volume":"90","author":"Borst","year":"2016","journal-title":"J. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"12221","DOI":"10.1128\/JVI.02382-15","article-title":"Human Cytomegalovirus Pul93 Is Required for Viral Genome Cleavage and Packaging","volume":"89","author":"DeRussy","year":"2015","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1128\/JVI.02766-15","article-title":"Involvement of the N-Terminal Deubiquitinating Protease Domain of Human Cytomegalovirus Ul48 Tegument Protein in Autoubiquitination, Virion Stability, and Virus Entry","volume":"90","author":"Kim","year":"2016","journal-title":"J. Virol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"9086","DOI":"10.1128\/JVI.01141-14","article-title":"Identification of Human Cytomegalovirus Genes Important for Biogenesis of the Cytoplasmic Virion Assembly Complex","volume":"88","author":"Das","year":"2014","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6005","DOI":"10.1128\/JVI.03558-12","article-title":"Nuclear Targeting of Human Cytomegalovirus Large Tegument Protein Pul48 Is Essential for Viral Growth","volume":"87","author":"Brock","year":"2013","journal-title":"J. Virol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jsb.2011.03.006","article-title":"Biochemical and Structural Characterization of the Capsid-Bound Tegument Proteins of Human Cytomegalovirus","volume":"174","author":"Yu","year":"2011","journal-title":"J. Struct. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"12198","DOI":"10.1128\/JVI.01280-12","article-title":"Identification of a Varicella-Zoster Virus Replication Inhibitor That Blocks Capsid Assembly by Interacting with the Floor Domain of the Major Capsid Protein","volume":"86","author":"Inoue","year":"2012","journal-title":"J. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Keil, T., Liu, D., Lloyd, M., Coombs, W., Moffat, J., and Visalli, R. (2020). DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01862"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/1913\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:04:02Z","timestamp":1760166242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/1913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,23]]},"references-count":119,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["v13101913"],"URL":"https:\/\/doi.org\/10.3390\/v13101913","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,23]]}}}