{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:09:21Z","timestamp":1790453361546,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1008961","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Varicella-zoster virus (VZV) is a medically important alphaherpesvirus that induces fusion of the virion envelope and the cell membrane during entry, and between cells to form polykaryocytes within infected tissues during pathogenesis. All members of the\n                    <jats:italic>Herpesviridae<\/jats:italic>\n                    , including VZV, have a conserved core fusion complex composed of glycoproteins, gB, gH and gL. The ectodomain of the primary fusogen, gB, has five domains, DI-V, of which DI contains the fusion loops needed for fusion function. We recently demonstrated that DIV is critical for fusion initiation, which was revealed by a 2.8\u00c5 structure of a VZV neutralizing mAb, 93k, bound to gB and mutagenesis of the gB-93k interface. To further assess the mechanism of mAb 93k neutralization, the binding site of a non-neutralizing mAb to gB, SG2, was compared to mAb 93k using single particle cryogenic electron microscopy (cryo-EM). The gB-SG2 interface partially overlapped with that of gB-93k but, unlike mAb 93k, mAb SG2 did not interact with the gB N-terminus, suggesting a potential role for the gB N-terminus in membrane fusion. The gB ectodomain structure in the absence of antibody was defined at near atomic resolution by single particle cryo-EM (3.9\u00c5) of native, full-length gB purified from infected cells and by X-ray crystallography (2.4\u00c5) of the transiently expressed ectodomain. Both structures revealed that the VZV gB N-terminus (aa72-114) was flexible based on the absence of visible structures in the cryo-EM or X-ray crystallography data but the presence of gB N-terminal peptides were confirmed by mass spectrometry. Notably, N-terminal residues\n                    <jats:sup>109<\/jats:sup>\n                    KSQD\n                    <jats:sup>112<\/jats:sup>\n                    were predicted to form a small \u03b1-helix and alanine substitution of these residues abolished cell-cell fusion in a virus-free assay. Importantly, transferring the\n                    <jats:sup>109<\/jats:sup>\n                    AAAA\n                    <jats:sup>112<\/jats:sup>\n                    mutation into the VZV genome significantly impaired viral propagation. These data establish a functional role for the gB N-terminus in membrane fusion broadly relevant to the\n                    <jats:italic>Herpesviridae<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1008961","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T18:36:49Z","timestamp":1610044609000},"page":"e1008961","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["The N-terminus of varicella-zoster virus glycoprotein B has a functional role in fusion"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-7310","authenticated-orcid":true,"given":"Stefan L.","family":"Oliver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2080-6146","authenticated-orcid":true,"given":"Yi","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5247-0106","authenticated-orcid":true,"given":"Dong-Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-7200","authenticated-orcid":true,"given":"Soung Hun","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0848-5335","authenticated-orcid":true,"given":"Grigore D.","family":"Pintilie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-8403","authenticated-orcid":true,"given":"David A.","family":"Bushnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8457-9061","authenticated-orcid":true,"given":"Marvin H.","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Carfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-3078","authenticated-orcid":true,"given":"Wah","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-1498","authenticated-orcid":true,"given":"Ann M.","family":"Arvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"ppat.1008961.ref001","first-page":"1803","volume-title":"Herpesviridae.","author":"PE Pellett","year":"2013","edition":"6"},{"issue":"8","key":"ppat.1008961.ref002","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1073\/pnas.0810530106","article-title":"Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B","volume":"106","author":"M Backovic","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"ppat.1008961.ref003","doi-asserted-by":"crossref","first-page":"e1005227","DOI":"10.1371\/journal.ppat.1005227","article-title":"Crystal Structure of the Human Cytomegalovirus Glycoprotein B.","volume":"11","author":"HG Burke","year":"2015","journal-title":"PLoS Pathog"},{"key":"ppat.1008961.ref004","doi-asserted-by":"crossref","first-page":"8176","DOI":"10.1038\/ncomms9176","article-title":"Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody","volume":"6","author":"S Chandramouli","year":"2015","journal-title":"Nat Commun"},{"issue":"5784","key":"ppat.1008961.ref005","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1126\/science.1126548","article-title":"Crystal structure of glycoprotein B from herpes simplex virus 1","volume":"313","author":"EE Heldwein","year":"2006","journal-title":"Science"},{"issue":"5784","key":"ppat.1008961.ref006","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1126\/science.1127683","article-title":"Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G","volume":"313","author":"S Roche","year":"2006","journal-title":"Science"},{"issue":"5813","key":"ppat.1008961.ref007","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1126\/science.1135710","article-title":"Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G","volume":"315","author":"S Roche","year":"2007","journal-title":"Science"},{"issue":"10","key":"ppat.1008961.ref008","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/nsmb.1484","article-title":"The postfusion structure of baculovirus gp64 supports a unified view of viral fusion machines","volume":"15","author":"J Kadlec","year":"2008","journal-title":"Nat Struct Mol Biol"},{"key":"ppat.1008961.ref009","article-title":"The structural basis of herpesvirus entry","author":"SA Connolly","year":"2020","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1008961.ref010","first-page":"2016","volume-title":"Varicella Zoster Virus.","author":"AM Arvin","year":"2013","edition":"6"},{"issue":"15","key":"ppat.1008961.ref011","doi-asserted-by":"crossref","first-page":"7495","DOI":"10.1128\/JVI.00400-09","article-title":"Mutagenesis of varicella-zoster virus glycoprotein B: putative fusion loop residues are essential for viral replication, and the furin cleavage motif contributes to pathogenesis in skin tissue in vivo","volume":"83","author":"SL Oliver","year":"2009","journal-title":"J Virol"},{"issue":"4","key":"ppat.1008961.ref012","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1093\/infdis\/148.4.630","article-title":"Common expression of varicella-zoster viral glycoprotein antigens in vitro and in chickenpox and zoster vesicles","volume":"148","author":"KA Weigle","year":"1983","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1008961.ref013","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1128\/IAI.19.1.199-203.1978","article-title":"Varicella-zoster virus: isolation and propagation in human melanoma cells at 36 and 32 degrees C","volume":"19","author":"C Grose","year":"1978","journal-title":"Infect Immun"},{"issue":"11","key":"ppat.1008961.ref014","doi-asserted-by":"crossref","first-page":"e1009022","DOI":"10.1371\/journal.ppat.1009022","article-title":"Calcineurin phosphatase activity regulates Varicella-Zoster Virus induced cell-cell fusion.","volume":"16","author":"M Zhou","year":"2020","journal-title":"PLOS Pathogens."},{"issue":"1","key":"ppat.1008961.ref015","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01613-16","article-title":"Dysregulated Glycoprotein B-Mediated Cell-Cell Fusion Disrupts Varicella-Zoster Virus and Host Gene Transcription during Infection","volume":"91","author":"SL Oliver","year":"2017","journal-title":"J Virol"},{"issue":"8","key":"ppat.1008961.ref016","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1128\/JVI.02592-07","article-title":"Mechanisms of varicella-zoster virus neuropathogenesis in human dorsal root ganglia","volume":"82","author":"M Reichelt","year":"2008","journal-title":"J Virol"},{"issue":"Suppl 1","key":"ppat.1008961.ref017","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1093\/infdis\/jiu542","article-title":"Varicella Zoster Virus in Temporal Arteries of Patients With Giant Cell Arteritis","volume":"212","author":"D Gilden","year":"2015","journal-title":"J Infect Dis"},{"issue":"12","key":"ppat.1008961.ref018","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1093\/infdis\/jiw101","article-title":"Varicella Zoster Virus Infection in Granulomatous Arteritis of the Aorta","volume":"213","author":"D Gilden","year":"2016","journal-title":"J Infect Dis"},{"issue":"19","key":"ppat.1008961.ref019","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1212\/WNL.0000000000001409","article-title":"Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis","volume":"84","author":"D Gilden","year":"2015","journal-title":"Neurology"},{"issue":"2","key":"ppat.1008961.ref020","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1073\/pnas.0913351107","article-title":"Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses","volume":"107","author":"T Suenaga","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"45","key":"ppat.1008961.ref021","doi-asserted-by":"crossref","first-page":"18412","DOI":"10.1073\/pnas.1111333108","article-title":"Structure-function analysis of varicella-zoster virus glycoprotein H identifies domain-specific roles for fusion and skin tropism","volume":"108","author":"SE Vleck","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"16","key":"ppat.1008961.ref022","doi-asserted-by":"crossref","first-page":"7567","DOI":"10.1128\/JVI.00792-16","article-title":"Role for the alphaV Integrin Subunit in Varicella-Zoster Virus-Mediated Fusion and Infection","volume":"90","author":"E Yang","year":"2016","journal-title":"J Virol"},{"issue":"5","key":"ppat.1008961.ref023","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1073\/pnas.1216985110","article-title":"An immunoreceptor tyrosine-based inhibition motif in varicella-zoster virus glycoprotein B regulates cell fusion and skin pathogenesis","volume":"110","author":"SL Oliver","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1008961.ref024","article-title":"The Glycoprotein B Cytoplasmic Domain Lysine Cluster Is Critical for Varicella Zoster Virus Cell-Cell Fusion Regulation and Infection","author":"E Yang","year":"2016","journal-title":"J Virol"},{"issue":"10","key":"ppat.1008961.ref025","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.1128\/JVI.00206-10","article-title":"Syncytial phenotype of C-terminally truncated herpes simplex virus type 1 gB is associated with diminished membrane interactions","volume":"84","author":"TK Chowdary","year":"2010","journal-title":"J Virol"},{"issue":"1","key":"ppat.1008961.ref026","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0168-1702(03)00070-4","article-title":"A single amino acid substitution in the cytoplasmic tail of the glycoprotein B of herpes simplex virus 1 affects both syncytium formation and binding to intracellular heparan sulfate","volume":"93","author":"A Diakidi-Kosta","year":"2003","journal-title":"Virus research"},{"issue":"4","key":"ppat.1008961.ref027","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1128\/JVI.67.4.2191-2201.1993","article-title":"Syncytium-inducing mutations localize to two discrete regions within the cytoplasmic domain of herpes simplex virus type 1 glycoprotein B","volume":"67","author":"PJ Gage","year":"1993","journal-title":"J Virol"},{"issue":"1","key":"ppat.1008961.ref028","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1006\/viro.2001.1141","article-title":"Different functional domains in the cytoplasmic tail of glycoprotein B are involved in Epstein-Barr virus-induced membrane fusion","volume":"290","author":"KM Haan","year":"2001","journal-title":"Virology"},{"issue":"1","key":"ppat.1008961.ref029","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1006\/viro.1993.1013","article-title":"Two novel single amino acid syncytial mutations in the carboxy terminus of glycoprotein B of herpes simplex virus type 1 confer a unique pathogenic phenotype","volume":"192","author":"JP Engel","year":"1993","journal-title":"Virology"},{"issue":"4","key":"ppat.1008961.ref030","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1128\/JVI.65.4.1770-1778.1991","article-title":"Altered pathogenesis in herpes simplex virus type 1 infection due to a syncytial mutation mapping to the carboxy terminus of glycoprotein B","volume":"65","author":"JL Goodman","year":"1991","journal-title":"J Virol"},{"issue":"1","key":"ppat.1008961.ref031","doi-asserted-by":"crossref","first-page":"e00571","DOI":"10.1128\/mBio.00571-12","article-title":"Modulation of Epstein-Barr virus glycoprotein B (gB) fusion activity by the gB cytoplasmic tail domain.","volume":"4","author":"NJ Garcia","year":"2013","journal-title":"MBio"},{"issue":"6","key":"ppat.1008961.ref032","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00429-12","article-title":"The membrane-proximal region (MPR) of herpes simplex virus gB regulates association of the fusion loops with lipid membranes.","volume":"3","author":"SS Shelly","year":"2012","journal-title":"MBio"},{"issue":"1","key":"ppat.1008961.ref033","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1038\/s41467-020-17911-0","article-title":"A glycoprotein B-neutralizing antibody structure at 2.8 A uncovers a critical domain for herpesvirus fusion initiation.","volume":"11","author":"SL Oliver","year":"2020","journal-title":"Nat Commun."},{"key":"ppat.1008961.ref034","article-title":"Structure-function dissection of the Pseudorabies virus glycoprotein B fusion loops","author":"M Vallbracht","year":"2017","journal-title":"J Virol"},{"issue":"5","key":"ppat.1008961.ref035","doi-asserted-by":"crossref","first-page":"e1004173","DOI":"10.1371\/journal.ppat.1004173","article-title":"The cytoplasmic domain of varicella-zoster virus glycoprotein H regulates syncytia formation and skin pathogenesis.","volume":"10","author":"E Yang","year":"2014","journal-title":"PLoS Pathog."},{"issue":"9","key":"ppat.1008961.ref036","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1128\/JVI.02596-10","article-title":"Mutagenesis of varicella-zoster virus glycoprotein I (gI) identifies a cysteine residue critical for gE\/gI heterodimer formation, gI structure, and virulence in skin cells.","volume":"85","author":"SL Oliver","year":"2011","journal-title":"J Virol"},{"issue":"39","key":"ppat.1008961.ref037","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abc1726","article-title":"The prefusion structure of herpes simplex virus glycoprotein B","volume":"6","author":"B Vollmer","year":"2020","journal-title":"Sci Adv"},{"issue":"12","key":"ppat.1008961.ref038","doi-asserted-by":"crossref","first-page":"e1007452","DOI":"10.1371\/journal.ppat.1007452","article-title":"Different functional states of fusion protein gB revealed on human cytomegalovirus by cryo electron tomography with Volta phase plate.","volume":"14","author":"Z Si","year":"2018","journal-title":"PLoS Pathog."},{"issue":"15","key":"ppat.1008961.ref039","doi-asserted-by":"crossref","first-page":"4176","DOI":"10.1073\/pnas.1523234113","article-title":"Two distinct trimeric conformations of natively membrane-anchored full-length herpes simplex virus 1 glycoprotein B","volume":"113","author":"T Zeev-Ben-Mordehai","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1008961.ref040","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/s41594-018-0060-6","article-title":"Structural basis for membrane anchoring and fusion regulation of the herpes simplex virus fusogen gB","volume":"25","author":"RS Cooper","year":"2018","journal-title":"Nat Struct Mol Biol"},{"issue":"32","key":"ppat.1008961.ref041","doi-asserted-by":"crossref","first-page":"13140","DOI":"10.1073\/pnas.0705926104","article-title":"Random linker-insertion mutagenesis to identify functional domains of herpes simplex virus type 1 glycoprotein B","volume":"104","author":"E Lin","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1008961.ref042","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1128\/JVI.03200-13","article-title":"Mechanism of neutralization of herpes simplex virus by antibodies directed at the fusion domain of glycoprotein B","volume":"88","author":"TM Cairns","year":"2014","journal-title":"J Virol"},{"issue":"1","key":"ppat.1008961.ref043","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0042-6822(89)90102-5","article-title":"Domain structure of herpes simplex virus 1 glycoprotein B: neutralizing epitopes map in regions of continuous and discontinuous residues","volume":"172","author":"L Pereira","year":"1989","journal-title":"Virology"},{"issue":"1","key":"ppat.1008961.ref044","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0042-6822(92)90064-V","article-title":"Domains of herpes simplex virus I glycoprotein B that function in virus penetration, cell-to-cell spread, and cell fusion","volume":"186","author":"D Navarro","year":"1992","journal-title":"Virology"},{"issue":"1","key":"ppat.1008961.ref045","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1128\/JVI.59.1.142-153.1986","article-title":"Antigenic variation (mar mutations) in herpes simplex virus glycoprotein B can induce temperature-dependent alterations in gB processing and virus production.","volume":"59","author":"SD Marlin","year":"1986","journal-title":"J Virol"},{"issue":"2","key":"ppat.1008961.ref046","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1128\/JVI.63.2.730-738.1989","article-title":"Identification of mar mutations in herpes simplex virus type 1 glycoprotein B which alter antigenic structure and function in virus penetration","volume":"63","author":"SL Highlander","year":"1989","journal-title":"J Virol"},{"issue":"6","key":"ppat.1008961.ref047","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1093\/infdis\/163.6.1344","article-title":"Human monoclonal antibodies neutralizing cytomegalovirus (CMV) for prophylaxis of CMV disease: report of a phase I trial in bone marrow transplant recipients.","volume":"163","author":"WE Aulitzky","year":"1991","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1008961.ref048","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1128\/JVI.67.2.703-710.1993","article-title":"Fine specificity of the human immune response to the major neutralization epitopes expressed on cytomegalovirus gp58\/116 (gB), as determined with human monoclonal antibodies.","volume":"67","author":"M Ohlin","year":"1993","journal-title":"J Virol"},{"issue":"8","key":"ppat.1008961.ref049","doi-asserted-by":"crossref","first-page":"e1002172","DOI":"10.1371\/journal.ppat.1002172","article-title":"B cell repertoire analysis identifies new antigenic domains on glycoprotein B of human cytomegalovirus which are target of neutralizing antibodies","volume":"7","author":"S Potzsch","year":"2011","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1008961.ref050","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1006\/viro.1996.0040","article-title":"Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures.","volume":"216","author":"K Schoppel","year":"1996","journal-title":"Virology"},{"issue":"2","key":"ppat.1008961.ref051","doi-asserted-by":"crossref","first-page":"460","DOI":"10.4161\/mabs.27760","article-title":"Multiplexed screening of natural humoral immunity identifies antibodies at fine specificity for complex and dynamic viral targets","volume":"6","author":"KM McCutcheon","year":"2014","journal-title":"MAbs"},{"issue":"43","key":"ppat.1008961.ref052","doi-asserted-by":"crossref","first-page":"73654","DOI":"10.18632\/oncotarget.18359","article-title":"Active evolution of memory B-cells specific to viral gH\/gL\/pUL128\/130\/131 pentameric complex in healthy subjects with silent human cytomegalovirus infection.","volume":"8","author":"L Xia","year":"2017","journal-title":"Oncotarget"},{"issue":"Pt 10","key":"ppat.1008961.ref053","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1099\/0022-1317-71-10-2443","article-title":"The gp116 of the gp58\/116 complex of human cytomegalovirus represents the amino-terminal part of the precursor molecule and contains a neutralizing epitope","volume":"71","author":"H Meyer","year":"1990","journal-title":"J Gen Virol"},{"issue":"13","key":"ppat.1008961.ref054","doi-asserted-by":"crossref","first-page":"6175","DOI":"10.1128\/JVI.00119-11","article-title":"Capturing the herpes simplex virus core fusion complex (gB-gH\/gL) in an acidic environment.","volume":"85","author":"TM Cairns","year":"2011","journal-title":"J Virol"},{"issue":"8","key":"ppat.1008961.ref055","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1128\/JVI.02710-06","article-title":"Antigenic and mutational analyses of herpes simplex virus glycoprotein B reveal four functional regions","volume":"81","author":"FC Bender","year":"2007","journal-title":"J Virol"},{"issue":"1","key":"ppat.1008961.ref056","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/s41467-020-14398-7","article-title":"Structure of the prefusion-locking broadly neutralizing antibody RVC20 bound to the rabies virus glycoprotein.","volume":"11","author":"J Hellert","year":"2020","journal-title":"Nat Commun."},{"issue":"6136","key":"ppat.1008961.ref057","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1126\/science.1234914","article-title":"Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody","volume":"340","author":"JS McLellan","year":"2013","journal-title":"Science"},{"issue":"6243","key":"ppat.1008961.ref058","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1126\/science.aaa8651","article-title":"DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers","volume":"349","author":"G Fibriansah","year":"2015","journal-title":"Science"},{"issue":"4","key":"ppat.1008961.ref059","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01268-17","article-title":"The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane.","volume":"8","author":"J Fontana","year":"2017","journal-title":"mBio"},{"issue":"23","key":"ppat.1008961.ref060","doi-asserted-by":"crossref","first-page":"13200","DOI":"10.1128\/JVI.01148-07","article-title":"A self-excisable infectious bacterial artificial chromosome clone of varicella-zoster virus allows analysis of the essential tegument protein encoded by ORF9","volume":"81","author":"BK Tischer","year":"2007","journal-title":"J Virol"},{"issue":"Suppl 1","key":"ppat.1008961.ref061","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1002\/jmv.10324","article-title":"Identification of the authentic varicella-zoster virus gB (gene 31) initiating methionine overlapping the 3' end of gene 30.","volume":"70","author":"L Maresova","year":"2003","journal-title":"J Med Virol"},{"issue":"1","key":"ppat.1008961.ref062","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0042-6822(84)90098-9","article-title":"Varicella-zoster virus-specific gp140: a highly immunogenic and disulfide-linked structural glycoprotein","volume":"132","author":"C Grose","year":"1984","journal-title":"Virology"},{"issue":"1","key":"ppat.1008961.ref063","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jsb.2005.07.007","article-title":"Automated electron microscope tomography using robust prediction of specimen movements","volume":"152","author":"DN Mastronarde","year":"2005","journal-title":"J Struct Biol"},{"issue":"4","key":"ppat.1008961.ref064","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nmeth.4193","article-title":"MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy.","volume":"14","author":"SQ Zheng","year":"2017","journal-title":"Nat Methods."},{"issue":"2","key":"ppat.1008961.ref065","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","article-title":"CTFFIND4: Fast and accurate defocus estimation from electron micrographs","volume":"192","author":"A Rohou","year":"2015","journal-title":"J Struct Biol"},{"issue":"1","key":"ppat.1008961.ref066","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jsb.2006.05.009","article-title":"EMAN2: an extensible image processing suite for electron microscopy","volume":"157","author":"G Tang","year":"2007","journal-title":"J Struct Biol"},{"issue":"3","key":"ppat.1008961.ref067","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","article-title":"RELION: implementation of a Bayesian approach to cryo-EM structure determination","volume":"180","author":"SH Scheres","year":"2012","journal-title":"J Struct Biol"},{"key":"ppat.1008961.ref068","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.42166","article-title":"New tools for automated high-resolution cryo-EM structure determination in RELION-3.","volume":"7","author":"J Zivanov","year":"2018","journal-title":"Elife"},{"issue":"2","key":"ppat.1008961.ref069","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.str.2011.12.014","article-title":"Outcome of the first electron microscopy validation task force meeting","volume":"20","author":"R Henderson","year":"2012","journal-title":"Structure"},{"issue":"Pt 4","key":"ppat.1008961.ref070","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"P Emsley","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 2","key":"ppat.1008961.ref071","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"PD Adams","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"1","key":"ppat.1008961.ref072","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and better reference data for improved all-atom structure validation","volume":"27","author":"CJ Williams","year":"2018","journal-title":"Protein Sci"},{"issue":"Pt 9","key":"ppat.1008961.ref073","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1107\/S2059798318009324","article-title":"New tools for the analysis and validation of cryo-EM maps and atomic models","volume":"74","author":"PV Afonine","year":"2018","journal-title":"Acta Crystallogr D Struct Biol"},{"issue":"1","key":"ppat.1008961.ref074","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nmeth.2727","article-title":"Quantifying the local resolution of cryo-EM density maps.","volume":"11","author":"A Kucukelbir","year":"2014","journal-title":"Nat Methods."},{"issue":"3","key":"ppat.1008961.ref075","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.jsb.2018.08.015","article-title":"Assessment of structural features in Cryo-EM density maps using SSE and side chain Z-scores","volume":"204","author":"G Pintilie","year":"2018","journal-title":"J Struct Biol"},{"issue":"3","key":"ppat.1008961.ref076","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/s41592-020-0731-1","article-title":"Measurement of atom resolvability in cryo-EM maps with Q-scores.","volume":"17","author":"G Pintilie","year":"2020","journal-title":"Nat Methods."},{"issue":"13","key":"ppat.1008961.ref077","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":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"},{"issue":"3","key":"ppat.1008961.ref078","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nmeth1019","article-title":"Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry.","volume":"4","author":"JE Elias","year":"2007","journal-title":"Nat Methods"},{"key":"ppat.1008961.ref079","first-page":"495","volume-title":"Using antibodies: a laboratory manual.","author":"E Harlow","year":"1999"},{"issue":"19","key":"ppat.1008961.ref080","doi-asserted-by":"crossref","first-page":"9481","DOI":"10.1128\/JVI.00533-06","article-title":"Essential functions of the unique N-terminal region of the varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection","volume":"80","author":"B Berarducci","year":"2006","journal-title":"J Virol"},{"issue":"1","key":"ppat.1008961.ref081","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1128\/JVI.00913-08","article-title":"Deletion of the first cysteine-rich region of the varicella-zoster virus glycoprotein E ectodomain abolishes the gE and gI interaction and differentially affects cell-cell spread and viral entry","volume":"83","author":"B Berarducci","year":"2009","journal-title":"J Virol"},{"issue":"1","key":"ppat.1008961.ref082","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1073\/pnas.0912373107","article-title":"Functions of the unique N-terminal region of glycoprotein E in the pathogenesis of varicella-zoster virus infection","volume":"107","author":"B Berarducci","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"W1","key":"ppat.1008961.ref083","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes","volume":"46","author":"A Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"ppat.1008961.ref084","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1021\/acs.jctc.8b01066","article-title":"CHARMM-GUI Membrane Builder for Complex Biological Membrane Simulations with Glycolipids and Lipoglycans.","volume":"15","author":"J Lee","year":"2019","journal-title":"J Chem Theory Comput."},{"issue":"2","key":"ppat.1008961.ref085","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1006\/viro.1994.1252","article-title":"The phospholipid composition of extracellular herpes simplex virions differs from that of host cell nuclei","volume":"200","author":"IL van Genderen","year":"1994","journal-title":"Virology"},{"issue":"4","key":"ppat.1008961.ref086","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.bpj.2015.11.3522","article-title":"Resolution and Probabilistic Models of Components in CryoEM Maps of Mature P22 Bacteriophage.","volume":"110","author":"G Pintilie","year":"2016","journal-title":"Biophys J"},{"issue":"24","key":"ppat.1008961.ref087","doi-asserted-by":"crossref","first-page":"12924","DOI":"10.1128\/JVI.01750-10","article-title":"Structural basis of local, pH-dependent conformational changes in glycoprotein B from herpes simplex virus type 1","volume":"84","author":"SD Stampfer","year":"2010","journal-title":"J Virol"},{"issue":"34","key":"ppat.1008961.ref088","doi-asserted-by":"crossref","first-page":"16856","DOI":"10.1073\/pnas.1821309116","article-title":"Distance-based protein folding powered by deep learning","volume":"116","author":"J. Xu","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"19","key":"ppat.1008961.ref089","doi-asserted-by":"crossref","first-page":"6056","DOI":"10.1073\/pnas.1501176112","article-title":"A site of varicella-zoster virus vulnerability identified by structural studies of neutralizing antibodies bound to the glycoprotein complex gHgL","volume":"112","author":"Y Xing","year":"2015","journal-title":"Proc Natl Acad Sci U S A"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1008961","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1008961","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T14:42:39Z","timestamp":1611153759000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1008961"}},"subtitle":[],"editor":[{"given":"Richard","family":"Longnecker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,7]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1008961","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.09.08.269191","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,7]]}}}