{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:11:42Z","timestamp":1767845502540,"version":"3.49.0"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,9]],"date-time":"2022-07-09T00:00:00Z","timestamp":1657324800000},"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":["R01AI128912"],"award-info":[{"award-number":["R01AI128912"]}],"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":["P26420-B13"],"award-info":[{"award-number":["P26420-B13"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["R01AI128912"],"award-info":[{"award-number":["R01AI128912"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P26420-B13"],"award-info":[{"award-number":["P26420-B13"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human cytomegalovirus (CMV) utilizes different glycoproteins to enter into fibroblast and epithelial cells. A trimer of glycoproteins H, L, and O (gH\/gL\/gO) is required for entry into all cells, whereas a pentamer of gH\/gL\/UL128\/UL130\/UL131A is selectively required for infection of epithelial, endothelial, and some myeloid-lineage cells, but not of fibroblasts. Both complexes are of considerable interest for vaccine and immunotherapeutic development but present a conundrum: gH\/gL-specific antibodies have moderate potency yet neutralize CMV entry into all cell types, whereas pentamer-specific antibodies are more potent but do not block fibroblast infection. Which cell types and neutralizing activities are important for protective efficacy in vivo remain unclear. Here, we present evidence that certain CMV strains have evolved polymorphisms in gO to evade trimer-specific neutralizing antibodies. Using luciferase-tagged variants of strain TB40\/E in which the native gO is replaced by gOs from other strains, we tested the effects of gO polymorphisms on neutralization by monoclonal antibodies (mAbs) targeting four independent epitopes in gH\/gL that are common to both trimer and pentamer. Neutralization of fibroblast entry by three mAbs displayed a range of potencies that depended on the gO type, a fourth mAb failed to neutralize fibroblast entry regardless of the gO type, while neutralization of epithelial cell entry by all four mAbs was potent and independent of the gO type. Thus, specific polymorphisms in gO protect the virus from mAb neutralization in the context of fibroblast but not epithelial cell entry. No influence of gO type was observed for protection against CMV hyperimmune globulin or CMV-seropositive human sera, suggesting that antibodies targeting protected gH\/gL epitopes represent a minority of the polyclonal neutralizing repertoire induced by natural infection.<\/jats:p>","DOI":"10.3390\/v14071508","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:06:21Z","timestamp":1657497981000},"page":"1508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Polymorphic Forms of Human Cytomegalovirus Glycoprotein O Protect against Neutralization of Fibroblast Entry by Antibodies Targeting Epitopes Defined by Glycoproteins H and L"],"prefix":"10.3390","volume":"14","author":[{"given":"Li","family":"He","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Taylor","sequence":"additional","affiliation":[{"name":"School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Costa","sequence":"additional","affiliation":[{"name":"School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1936-0404","authenticated-orcid":false,"given":"Irene","family":"G\u00f6rzer","sequence":"additional","affiliation":[{"name":"Center for Virology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9872-3367","authenticated-orcid":false,"given":"Julia","family":"Kalser","sequence":"additional","affiliation":[{"name":"Center for Virology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-2271","authenticated-orcid":false,"given":"Tong-Ming","family":"Fu","sequence":"additional","affiliation":[{"name":"Texas Therapeutic Institute, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Freed","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Rahway, NJ 07065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dai","family":"Wang","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Rahway, NJ 07065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-1254","authenticated-orcid":false,"given":"Laura","family":"Hertel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, Oakland, CA 94609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-7870","authenticated-orcid":false,"given":"Michael A.","family":"McVoy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/rmv.695","article-title":"Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection","volume":"21","author":"Cannon","year":"2011","journal-title":"Rev. Med. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/CMR.00062-12","article-title":"The \u201csilent\u201d global burden of congenital cytomegalovirus","volume":"26","author":"Manicklal","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/rmv.535","article-title":"Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection","volume":"17","author":"Kenneson","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2807\/ese.14.09.19140-en","article-title":"Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe","volume":"14","author":"Ludwig","year":"2009","journal-title":"Euro Surveill."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1093\/jpids\/piu069","article-title":"Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection","volume":"3","author":"Pass","year":"2014","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/rmv.544","article-title":"New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection","volume":"17","author":"Dollard","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1128\/CMR.00009-10","article-title":"Antiviral drug resistance of human cytomegalovirus","volume":"23","author":"Lurain","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1086\/507634","article-title":"Placental enlargement in women with primary maternal cytomegalovirus infection is associated with fetal and neonatal disease","volume":"43","author":"Nigro","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/pd.2013","article-title":"Regression of fetal cerebral abnormalities by primary cytomegalovirus infection following hyperimmunoglobulin therapy","volume":"28","author":"Nigro","year":"2008","journal-title":"Prenat. Diagn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.2353\/ajpath.2010.091210","article-title":"Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection","volume":"177","author":"Maidji","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1006\/viro.1993.1192","article-title":"Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate","volume":"193","author":"Compton","year":"1993","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1099\/0022-1317-74-2-255","article-title":"Structure, composition and heparin binding properties of a human cytomegalovirus glycoprotein complex designated gC-II","volume":"74","author":"Kari","year":"1993","journal-title":"J. Gen. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.tcb.2003.10.009","article-title":"Receptors and immune sensors: The complex entry path of human cytomegalovirus","volume":"14","author":"Compton","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8999","DOI":"10.1128\/JVI.01325-15","article-title":"Human Cytomegalovirus gH\/gL\/gO Promotes the Fusion Step of Entry into All Cell Types, whereas gH\/gL\/UL128-131 Broadens Virus Tropism through a Distinct Mechanism","volume":"89","author":"Zhou","year":"2015","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18153","DOI":"10.1073\/pnas.0509201102","article-title":"Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism","volume":"102","author":"Wang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1128\/JVI.02249-09","article-title":"A human cytomegalovirus gO-null mutant fails to incorporate gH\/gL into the virion envelope and is unable to enter fibroblasts and epithelial and endothelial cells","volume":"84","author":"Wille","year":"2010","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00332-13","DOI":"10.1128\/mBio.00332-13","article-title":"Human cytomegalovirus (HCMV) glycoprotein gB promotes virus entry in trans acting as the viral fusion protein rather than as a receptor-binding protein","volume":"4","author":"Wille","year":"2013","journal-title":"mBio"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coviro.2016.01.010","article-title":"gH\/gL supercomplexes at early stages of herpesvirus entry","volume":"18","author":"Heldwein","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1128\/JVI.80.2.710-722.2006","article-title":"Human cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion","volume":"80","author":"Ryckman","year":"2006","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1128\/MMBR.00018-16","article-title":"Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: A Sticky Virus Makes a Slick Getaway","volume":"80","author":"Gardner","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1128\/JVI.01809-09","article-title":"Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH\/gL\/UL128-131A complex","volume":"84","author":"Macagno","year":"2010","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6216","DOI":"10.1128\/JVI.00121-16","article-title":"Monoclonal Antibodies to Different Components of the Human Cytomegalovirus (HCMV) Pentamer gH\/gL\/pUL128L and Trimer gH\/gL\/gO as well as Antibodies Elicited during Primary HCMV Infection Prevent Epithelial Cell Syncytium Formation","volume":"90","author":"Gerna","year":"2016","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17965","DOI":"10.1073\/pnas.1415310111","article-title":"Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies","volume":"111","author":"Kabanova","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E4997","DOI":"10.1073\/pnas.1316517110","article-title":"Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine","volume":"110","author":"Freed","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1016\/j.vaccine.2007.01.011","article-title":"DNA vaccines expressing glycoprotein complex II antigens gM and gN elicited neutralizing antibodies against multiple human cytomegalovirus (HCMV) isolates","volume":"25","author":"Shen","year":"2007","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1128\/CVI.00092-12","article-title":"Strain-specific neutralizing antibody responses against human cytomegalovirus envelope glycoprotein N","volume":"19","author":"Pati","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16082","DOI":"10.1038\/nmicrobiol.2016.82","article-title":"Platelet-derived growth factor-\u03b1 receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer","volume":"1","author":"Kabanova","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8191","DOI":"10.1128\/JVI.72.10.8191-8197.1998","article-title":"The human cytomegalovirus UL74 gene encodes the third component of the glycoprotein H-glycoprotein L-containing envelope complex","volume":"72","author":"Huber","year":"1998","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.virol.2003.09.036","article-title":"Linkage of human cytomegalovirus glycoprotein gO variant groups identified from worldwide clinical isolates with gN genotypes, implications for disease associations and evidence for N-terminal sites of positive selection","volume":"318","author":"Mattick","year":"2004","journal-title":"Virology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10841","DOI":"10.1128\/JVI.76.21.10841-10848.2002","article-title":"The genes encoding the gCIII complex of human cytomegalovirus exist in highly diverse combinations in clinical isolates","volume":"76","author":"Rasmussen","year":"2002","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1006\/viro.2001.1274","article-title":"A role for human cytomegalovirus glycoprotein O (gO) in cell fusion and a new hypervariable locus","volume":"293","author":"Paterson","year":"2002","journal-title":"Virology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e01650-16","DOI":"10.1128\/JVI.01650-16","article-title":"Impact of Antibodies and Strain Polymorphisms on Cytomegalovirus Entry and Spread in Fibroblasts and Epithelial Cells","volume":"91","author":"Cui","year":"2017","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e02051-19","DOI":"10.1128\/JVI.02051-19","article-title":"Polymorphisms in Human Cytomegalovirus Glycoprotein O (gO) Exert Epistatic Influences on Cell-Free and Cell-to-Cell Spread and Antibody Neutralization on gH Epitopes","volume":"94","author":"Day","year":"2020","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e02033-16","DOI":"10.1128\/JVI.02033-16","article-title":"Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH\/gL\/pUL128-131 Pentameric Complex","volume":"91","author":"Ha","year":"2017","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.cell.2021.01.036","article-title":"Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry","volume":"184","author":"Kschonsak","year":"2021","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1128\/AAC.04295-14","article-title":"A high-affinity native human antibody neutralizes human cytomegalovirus infection of diverse cell types","volume":"59","author":"Kauvar","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.vaccine.2009.01.006","article-title":"A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain)","volume":"27","author":"Jacobson","year":"2009","journal-title":"Vaccine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1099\/vir.0.83286-0","article-title":"Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40\/E","volume":"89","author":"Sinzger","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Scrivano, L., Sinzger, C., Nitschko, H., Koszinowski, U.H., and Adler, B. (2011). HCMV spread and cell tropism are determined by distinct virus populations. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1001256"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.3389\/fmicb.2017.01609","article-title":"Differences in Growth Properties among Two Human Cytomegalovirus Glycoprotein O Genotypes","volume":"8","author":"Kalser","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e00107-20","DOI":"10.1128\/JVI.00107-20","article-title":"Influence of Human Cytomegalovirus Glycoprotein O Polymorphism on the Inhibitory Effect of Soluble Forms of Trimer- and Pentamer-Specific Entry Receptors","volume":"94","author":"Brait","year":"2020","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1093\/nar\/gni035","article-title":"Simple and highly efficient BAC recombineering using galK selection","volume":"33","author":"Warming","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"428498","DOI":"10.1155\/2012\/428498","article-title":"Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine","volume":"2012","author":"Cui","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1128\/JVI.03062-13","article-title":"Human cytomegalovirus infection of langerhans-type dendritic cells does not require the presence of the gH\/gL\/UL128-131A complex and is blocked after nuclear deposition of viral genomes in immature cells","volume":"88","author":"Lauron","year":"2014","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1016\/j.vaccine.2011.01.079","article-title":"Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells","volume":"29","author":"Saccoccio","year":"2011","journal-title":"Vaccine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.antiviral.2013.07.016","article-title":"Ribonucleotide reductase inhibitors hydroxyurea, didox, and trimidox inhibit human cytomegalovirus replication in vitro and synergize with ganciclovir","volume":"100","author":"Bhave","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/infdis\/165.2.381","article-title":"Antibodies to recombinant-derived glycoprotein B after natural human cytomegalovirus infection correlate with neutralizing activity","volume":"165","author":"Marshall","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0264-410X(91)90187-B","article-title":"High expression of human cytomegalovirus (HCMV)-gB protein in cells infected with a vaccinia-gB recombinant: The importance of the gB protein in HCMV immunity","volume":"9","author":"Hirka","year":"1991","journal-title":"Vaccine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1128\/jvi.64.3.1079-1085.1990","article-title":"Cell surface expression of human cytomegalovirus (HCMV) gp55-116 (gB): Use of HCMV-recombinant vaccinia virus-infected cells in analysis of the human neutralizing antibody response","volume":"64","author":"Britt","year":"1990","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7444","DOI":"10.1128\/JVI.00467-12","article-title":"Antibodies against the gH\/gL\/UL128\/UL130\/UL131 complex comprise the majority of the anti-cytomegalovirus (anti-CMV) neutralizing antibody response in CMV hyperimmune globulin","volume":"86","author":"Fouts","year":"2012","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1517\/14656566.2.8.1247","article-title":"Cytomegalovirus treatment options in immunocompromised patients","volume":"2","author":"Sharland","year":"2001","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.antiviral.2011.03.179","article-title":"Cytomegalovirus reactivation in critically ill immunocompetent hosts: A decade of progress and remaining challenges","volume":"90","author":"Cook","year":"2011","journal-title":"Antiviral Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S754","DOI":"10.1093\/clinids\/12.Supplement_7.S754","article-title":"Impact of cytomegalovirus infection on organ transplant recipients","volume":"12","author":"Rubin","year":"1990","journal-title":"Rev. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Maingi, Z., and Nyamache, A.K. (2014). Seroprevalence of Cytomegalo Virus (CMV) among pregnant women in Thika, Kenya. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-794"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e02392-16","DOI":"10.1128\/JVI.02392-16","article-title":"Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity","volume":"91","author":"Britt","year":"2017","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1542\/peds.104.1.55","article-title":"Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus","volume":"104","author":"Boppana","year":"1999","journal-title":"Pediatrics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/S0140-6736(05)70487-6","article-title":"Simultaneous infection of healthy people with multiple human cytomegalovirus strains","volume":"352","author":"Ebert","year":"1998","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/infdis\/143.3.391","article-title":"Cytomegalovirus-specific humoral and cellular immune responses in human pregnancy","volume":"143","author":"Gehrz","year":"1981","journal-title":"J. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1056\/NEJM197706022962203","article-title":"Congenital cytomegalovirus infection","volume":"296","author":"Stagno","year":"1977","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJM197307052890101","article-title":"Maternal cytomegalovirus excretion and perinatal infection","volume":"289","author":"Reynolds","year":"1973","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1056\/NEJM200105033441804","article-title":"Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity","volume":"344","author":"Boppana","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1185350","article-title":"Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus","volume":"328","author":"Hansen","year":"2010","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1007\/s00705-011-1105-x","article-title":"UL74 of human cytomegalovirus reduces the inhibitory effect of gH-specific and gB-specific antibodies","volume":"156","author":"Jiang","year":"2011","journal-title":"Arch. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e0065721","DOI":"10.1128\/JVI.00657-21","article-title":"A Novel Strain-Specific Neutralizing Epitope on Glycoprotein H of Human Cytomegalovirus","volume":"95","author":"Thomas","year":"2021","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eabm2546","DOI":"10.1126\/sciadv.abm2546","article-title":"Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies","volume":"8","author":"Wrapp","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wu, Y., Prager, A., Boos, S., Resch, M., Brizic, I., Mach, M., Wildner, S., Scrivano, L., and Adler, B. (2017). Human cytomegalovirus glycoprotein complex gH\/gL\/gO uses PDGFR-\u03b1 as a key for entry. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006281"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e00138-19","DOI":"10.1128\/JVI.00138-19","article-title":"The N Terminus of Human Cytomegalovirus Glycoprotein O Is Important for Binding to the Cellular Receptor PDGFR\u03b1","volume":"93","author":"Stegmann","year":"2019","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kropff, B., Burkhardt, C., Schott, J., Nentwich, J., Fisch, T., Britt, W., and Mach, M. (2012). Glycoprotein N of human cytomegalovirus protects the virus from neutralizing antibodies. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002999"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"eabf3178","DOI":"10.1126\/sciadv.abf3178","article-title":"Prefusion structure of human cytomegalovirus glycoprotein B and structural basis for membrane fusion","volume":"7","author":"Liu","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Si, Z., Zhang, J., Shivakoti, S., Atanasov, I., Tao, C.L., Hui, W.H., Zhou, K., Yu, X., Li, W., and Luo, M. (2018). Different functional states of fusion protein gB revealed on human cytomegalovirus by cryo electron tomography with Volta phase plate. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007452"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eaan1457","DOI":"10.1126\/sciimmunol.aan1457","article-title":"Structural basis for potent antibody-mediated neutralization of human cytomegalovirus","volume":"2","author":"Chandramouli","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1016\/j.vaccine.2008.07.092","article-title":"Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection","volume":"26","author":"Cui","year":"2008","journal-title":"Vaccine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4591","DOI":"10.1128\/JVI.80.9.4591-4600.2006","article-title":"Human cytomegalovirus infection elicits a glycoprotein M (gM)\/gN-specific virus-neutralizing antibody response","volume":"80","author":"Shimamura","year":"2006","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/7\/1508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:47:15Z","timestamp":1760140035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/7\/1508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,9]]},"references-count":73,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["v14071508"],"URL":"https:\/\/doi.org\/10.3390\/v14071508","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,9]]}}}