{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:41:00Z","timestamp":1790091660757,"version":"4.0.1"},"reference-count":109,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for the sick, infant, elderly and immunocompromised\/immunodeficient individuals. Although traditional antiviral drugs (e.g., ganciclovir, valganciclovir, cidofovir, foscarnet) can be used to treat or prevent acute HCMV infections, their efficacy is limited because of toxicity, resistance issues, side effects and other problems. Fortunately, novel drugs (e.g., letermovir and maribavir) with less toxicity and drug\/cross-resistance have been approved and put on the market in recent years. The nucleic acid-based gene-targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPRs)\/CRISPRs-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) have been investigated to remove both lytic and latent CMV in vitro and\/or in vivo. Cell therapy including the adoptive T cell therapy (ACT) and immunotherapy have been tried against drug-resistant and recurrent HCMV in patients receiving hematopoietic stem cell transplantation (HSCT) or solid organ transplant (SOT), and they have also been used to treat glioblastoma (GBM) associated with HCMV infections. These newly developed antiviral strategies are expected to yield fruitful results and make a significant contribution to the treatment of HCMV infections. Despite this progress, the nucleic acid-based gene-targeting approaches are still under study for basic research, and cell therapy is adopted in a small study population size or only successful in case reports. Additionally, no current drugs have been approved to be indicated for latent infections. Therefore, the next strategy is to develop antiviral strategies to elevate efficacy against acute and\/or latent infections and overcome challenges such as toxicity, resistance issues, and side effects. In this review, we would explore the challenges, recent advances and perspectives in the treatment of HCMV infections. Furthermore, the suitable therapeutic strategies as well as the possibility for compassionate use would be evaluated.<\/jats:p>","DOI":"10.3390\/tropicalmed7120439","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T03:01:51Z","timestamp":1671073311000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections"],"prefix":"10.3390","volume":"7","author":[{"given":"Shiu-Jau","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mackay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatric, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 33004, Taiwan"},{"name":"Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Jenteh Junior College of Medicine, Nursing and Management, Miaoli County 35664, Taiwan"},{"name":"Program in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1128\/JVI.76.4.1537-1547.2002","article-title":"Herpesvirus assembly and egress","volume":"76","author":"Mettenleiter","year":"2002","journal-title":"J. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0147-9571(91)90123-U","article-title":"The glycoproteins of the human herpesviruses","volume":"14","author":"Manservigi","year":"1991","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_3","first-page":"7","article-title":"Persistent and recurring viral infections: The human herpesviruses","volume":"39","author":"Schleiss","year":"2009","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chen, S.J., Wang, S.C., and Chen, Y.C. (2019). Antiviral Agents as Therapeutic Strategies Against Cytomegalovirus Infections. Viruses, 12.","DOI":"10.3390\/v12010021"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41579-020-00448-w","article-title":"The structural basis of herpesvirus entry","volume":"19","author":"Connolly","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","first-page":"367","article-title":"The terminase complex, a relevant target for the treatment of HCMV infection","volume":"36","author":"Ligat","year":"2020","journal-title":"Med. Sci."},{"key":"ref_7","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_8","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_9","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1750-3639.2001.tb00415.x","article-title":"Human herpesvirus latency","volume":"11","author":"Cohrs","year":"2001","journal-title":"Brain Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1172\/JCI136225","article-title":"Herpesvirus latency","volume":"130","author":"Cohen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_11","first-page":"1","article-title":"Human cytomegalovirus genome","volume":"325","author":"Murphy","year":"2008","journal-title":"Curr. Top Microbiol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0163-7258(03)00034-2","article-title":"The human cytomegalovirus","volume":"98","author":"Landolfo","year":"2003","journal-title":"Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.coviro.2012.01.001","article-title":"Human cytomegalovirus entry into cells","volume":"2","author":"Vanarsdall","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1038\/s41467-019-10587-1","article-title":"CD46 facilitates entry and dissemination of human cytomegalovirus","volume":"10","author":"Stein","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gerna, G., Kabanova, A., and Lilleri, D. (2019). Human cytomegalovirus cell tropism and host cell receptors. Vaccines, 7.","DOI":"10.3390\/vaccines7030070"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nguyen, C.C., and Kamil, J.P. (2018). Pathogen at the gates: Human cytomegalovirus entry and cell tropism. Viruses, 10.","DOI":"10.20944\/preprints201811.0378.v2"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S111","DOI":"10.1016\/S1386-6532(02)00096-3","article-title":"Genetic analyses of gene function and pathogenesis of murine cytomegalovirus by transposon-mediated mutagenesis","volume":"25","author":"Lee","year":"2002","journal-title":"J. Clin. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7411","DOI":"10.1128\/JVI.74.16.7411-7421.2000","article-title":"Construction and characterization of murine cytomegaloviruses that contain transposon insertions at open reading frames M09 and M83","volume":"74","author":"Zhan","year":"2000","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1128\/AAC.44.6.1588-1597.2000","article-title":"Recombinant green fluorescent protein-expressing human cytomegalovirus as a tool for screening antiviral agents. Antimicrob","volume":"44","author":"Marschall","year":"2000","journal-title":"Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0166-3542(01)00126-7","article-title":"Inhibition of cytomegalovirus immediate early gene expression: A therapeutic option?","volume":"49","author":"Scholz","year":"2001","journal-title":"Antiviral. Res."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/path.4437","article-title":"The pathogenesis of human cytomegalovirus","volume":"235","author":"Griffiths","year":"2015","journal-title":"J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-0716-1111-1_1","article-title":"Overview of Human Cytomegalovirus Pathogenesis","volume":"2244","author":"Fulkerson","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"La, Y., Kwon, D.E., Yoo, S.G., Lee, K.H., Han, S.H., and Song, Y.G. (2019). Human cytomegalovirus seroprevalence and titers in solid organ transplant recipients and transplant donors in Seoul, South Korea. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4607-x"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.yexmp.2011.10.011","article-title":"Human cytomegalovirus and mucoepidermoid carcinoma of salivary glands: Cell-specific localization of active viral and oncogenic signaling proteins is confirmatory of a causal relationship","volume":"92","author":"Melnick","year":"2012","journal-title":"Exp. Mol. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/EDE.0000000000000844","article-title":"Herpesvirus Infection in Infants with Gastroschisis","volume":"29","author":"Francis","year":"2018","journal-title":"Epidemiology"},{"key":"ref_27","first-page":"213","article-title":"Congenital cytomegalovirus infection","volume":"95","author":"Leung","year":"2003","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/B978-0-444-53488-0.00015-8","article-title":"Congenital cytomegalovirus infection","volume":"123","author":"Bale","year":"2014","journal-title":"Handb. Clin. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/bdra.23601","article-title":"Cytomegalovirus infection in pregnancy","volume":"109","author":"Davis","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1097\/CM9.0000000000000404","article-title":"Congenital human cytomegalovirus infection and neurologic diseases in newborns","volume":"132","author":"Zhang","year":"2019","journal-title":"Chin. Med. J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Krstanovi\u0107, F., Britt, W.J., Jonji\u0107, S., and Brizi\u0107, I. (2021). Cytomegalovirus Infection and Inflammation in Developing Brain. Viruses, 13.","DOI":"10.3390\/v13061078"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, S.C., Chen, S.J., and Chen, Y.C. (2020). Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041376"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6643","DOI":"10.1158\/0008-5472.CAN-11-0744","article-title":"Human cytomegalovirus US28 found in glioblastoma promotes an invasive and angiogenic phenotype","volume":"71","author":"Soroceanu","year":"2011","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11908-017-0563-z","article-title":"The viral connection to glioblastoma","volume":"19","author":"Wen","year":"2017","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_35","first-page":"1671","article-title":"Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis","volume":"130","author":"Krenzlin","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1097\/NEN.0000000000000125","article-title":"Cytomegalovirus and glioblastoma: A review of evidence for their association and indications for testing and treatment","volume":"73","author":"Solomon","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s11060-015-1734-0","article-title":"Cytomegalovirus and glioblastoma; controversies and opportunities","volume":"123","author":"Lawler","year":"2015","journal-title":"J. Neurooncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.canlet.2021.05.005","article-title":"Cytomegalovirus infection of glioblastoma cells leads to NF-\u03baB dependent upregulation of the c-MET oncogenic tyrosine kinase","volume":"513","author":"Krenzlin","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yang, T., Liu, D., Fang, S., Ma, W., and Wang, Y. (2022). Cytomegalovirus and Glioblastoma: A Review of the Biological Associations and Therapeutic Strategies. J. Clin. Med., 11.","DOI":"10.3390\/jcm11175221"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1542\/pir.33.4.156","article-title":"Cytomegalovirus infection","volume":"33","author":"Plosa","year":"2012","journal-title":"Pediatr. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s40265-018-0943-1","article-title":"New Developments in the Management of Cytomegalovirus Infection After Transplantation","volume":"78","author":"Meesing","year":"2018","journal-title":"Drugs"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1182\/blood-2016-06-688432","article-title":"How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients","volume":"128","author":"Shah","year":"2016","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1111\/j.1600-6143.2007.01910.x","article-title":"Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients","volume":"7","author":"Asberg","year":"2007","journal-title":"Am. J. Transplant."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.3109\/14767058.2015.1058774","article-title":"Anti-viral therapy for congenital cytomegalovirus infection: Pharmacokinetics, efficacy and side effects","volume":"29","author":"Mareri","year":"2016","journal-title":"J. Matern. Fetal. Neonatal. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2165\/11316080-000000000-00000","article-title":"Antivirals for cytomegalovirus infection in neonates and infants: Focus on pharmacokinetics, formulations, dosing, and adverse events","volume":"11","author":"Marshall","year":"2009","journal-title":"Paediatr. Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1261\/rna.069682.118","article-title":"Inhibition of human cytomegalovirus major capsid protein expression and replication by ribonuclease P-associated external guide sequences","volume":"25","author":"Deng","year":"2019","journal-title":"RNA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5634","DOI":"10.7150\/thno.27776","article-title":"Engineered RNase P ribozymes effectively inhibit the infection of murine cytomegalovirus in animals","volume":"8","author":"Li","year":"2018","journal-title":"Theranostics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.omtn.2017.10.007","article-title":"Inhibition of murine cytomegalovirus infection in animals by RNase P-associated external guide sequences","volume":"9","author":"Li","year":"2017","journal-title":"Mol. Ther. Nucleic. Acids"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chen, Y.C., Sheng, J., Trang, P., and Liu, F. (2018). Potential Application of the CRISPR\/Cas9 System against Herpesvirus Infections. Viruses, 10.","DOI":"10.3390\/v10060291"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1007\/s00705-020-04687-3","article-title":"Targeting human cytomegalovirus IE genes by CRISPR\/Cas9 nuclease effectively inhibits viral replication and reactivation","volume":"165","author":"Xiao","year":"2020","journal-title":"Arch. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gergen, J., Coulon, F., Creneguy, A., Elain-Duret, N., Gutierrez, A., Pinkenburg, O., Verhoeyen, E., Anegon, I., Nguyen, T.H., and Halary, F.A. (2018). Multiplex CRISPR\/Cas9 system impairs HCMV replication by excising an essential viral gene. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192602"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"van Diemen, F.R., Kruse, E.M., Hooykaas, M.J., Bruggeling, C.E., Sch\u00fcrch, A.C., van Ham, P.M., Imhof, S.M., Nijhuis, M., Wiertz, E.J., and Lebbink, R.J. (2016). CRISPR\/Cas9-mediated genome editing of herpesviruses limits productive and latent Infections. PloS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005701"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Chen, S.J., and Chen, Y.C. (2019). Potential application of TALENs against murine cytomegalovirus latent infections. Viruses, 11.","DOI":"10.3390\/v11050414"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1080\/17425247.2018.1517746","article-title":"Delivery approaches for CRISPR\/Cas9 therapeutics in vivo: Advances and challenges","volume":"15","author":"Luther","year":"2018","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1080\/10717544.2018.1474964","article-title":"Delivering CRISPR: A review of the challenges and approaches","volume":"25","author":"Lino","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2019.01.017","article-title":"CRISPR-Cas9 for cancer therapy: Opportunities and challenges","volume":"447","author":"Chen","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.omtn.2019.02.027","article-title":"Genome-editing technologies: Concept, pros, and cons of various genome-editing techniques and bioethical concerns for clinical application","volume":"16","author":"Khan","year":"2019","journal-title":"Mol. Ther. Nucleic. Acids"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"BSR20200127","DOI":"10.1042\/BSR20200127","article-title":"Gene editing and CRISPR in the clinic: Current and future perspectives","volume":"40","author":"Hirakawa","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/CJI.0000000000000197","article-title":"Early experience with Clini MACS prodigy CCS (IFN-gamma) system in selection of virus specific T cells from third-party donors for pediatric patients with severe viral infections after hematopoietic stem cell transplantation","volume":"41","author":"Kallay","year":"2018","journal-title":"J. Immunother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1093\/cid\/ciy549","article-title":"Autologous adoptive T-cell therapy for recurrent or drug-resistant cytomegalovirus complications in solid organ transplant recipients: A single-arm open-label phase I clinical trial","volume":"68","author":"Smith","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.healun.2015.12.031","article-title":"Novel autologous T-cell therapy for drug-resistant cytomegalovirus disease after lung transplantation","volume":"35","author":"Pierucci","year":"2016","journal-title":"J. Heart Lung Transplant."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/ajt.13023","article-title":"Adoptive T cell immunotherapy for treatment of ganciclovir-resistant cytomegalovirus disease in a renal transplant recipient","volume":"15","author":"Macesic","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"135","DOI":"10.14791\/btrt.2022.0010","article-title":"Cytomegalovirus-Specific Immunotherapy for Glioblastoma Treatments","volume":"10","author":"Ahn","year":"2022","journal-title":"Brain Tumor. Res. Treat."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fonc.2014.00275","article-title":"Cytomegalovirus as a novel target for immunotherapy of glioblastoma multiforme","volume":"4","author":"Schuessler","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2217\/imt.16.2","article-title":"Cytomegalovirus-targeted immunotherapy and glioblastoma: Hype or hope?","volume":"8","author":"Ferguson","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jocn.2019.03.051","article-title":"Long-term glioblastoma survival following recovery from cytomegalovirus colitis: A case report","volume":"64","author":"Lamano","year":"2019","journal-title":"J. Clin. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1158\/1078-0432.CCR-16-2057","article-title":"Long-term survival in glioblastoma with cytomegalovirus pp65-targeted vaccination","volume":"23","author":"Batich","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1158\/1078-0432.CCR-13-3268","article-title":"Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells","volume":"20","author":"Nair","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e29289","DOI":"10.4161\/onci.29289","article-title":"Immunological targeting of cytomegalovirus for glioblastoma therapy","volume":"3","author":"Nair","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2017.10.019","article-title":"A third component of the human cytomegalovirus terminase complex is involved in letermovir resistance","volume":"148","author":"Chou","year":"2017","journal-title":"Antiviral. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/bmb\/ldz031","article-title":"Advances in the treatment of cytomegalovirus","volume":"131","author":"Krishna","year":"2019","journal-title":"Br. Med. Bull."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.2147\/IDR.S180908","article-title":"Letermovir for the prevention of cytomegalovirus infection and disease in transplant recipients: An evidence-based review","volume":"12","author":"Helou","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e13187","DOI":"10.1111\/tid.13187","article-title":"Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: Real-world experience","volume":"21","author":"Lin","year":"2019","journal-title":"Transpl. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e13166","DOI":"10.1111\/tid.13166","article-title":"Single-center experience with use of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients","volume":"21","author":"Aryal","year":"2019","journal-title":"Transpl. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1097\/TP.0000000000002886","article-title":"Letermovir for difficult to treat cytomegalovirus infection in lung transplant recipients","volume":"104","author":"Veit","year":"2019","journal-title":"Transplantation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.medmal.2018.03.006","article-title":"Maribavir, brincidofovir and letermovir: Efficacy and safety of new antiviral drugs for treating cytomegalovirus infections","volume":"48","author":"Frange","year":"2018","journal-title":"Med. Mal. Infect."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1093\/cid\/ciab988","article-title":"Maribavir for Refractory Cytomegalovirus Infections with or without Resistance Post-Transplant: Results from a Phase 3 Randomized Clinical Trial","volume":"75","author":"Avery","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMoa1714656","article-title":"Maribavir for Preemptive Treatment of Cytomegalovirus Reactivation","volume":"381","author":"Maertens","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/cid\/ciaa1713","article-title":"Letermovir and Maribavir for the Treatment and Prevention of Cytomegalovirus Infection in Solid Organ and Stem Cell Transplant Recipients","volume":"73","author":"Imlay","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1093\/cid\/ciy706","article-title":"Maribavir for Refractory or Resistant Cytomegalovirus Infections in Hematopoietic-cell or Solid-organ Transplant Recipients: A Randomized, Dose-ranging, Double-blind, Phase 2 Study","volume":"68","author":"Papanicolaou","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.bbmt.2018.09.038","article-title":"A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation","volume":"25","author":"Marty","year":"2019","journal-title":"Biol. Blood Marrow. Transplant."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/infdis\/jiw073","article-title":"Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis","volume":"214","author":"Lanier","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jcv.2019.04.007","article-title":"New vaccines and antiviral drugs for cytomegalovirus","volume":"116","author":"Griffiths","year":"2019","journal-title":"J. Clin. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"104710","DOI":"10.1016\/j.antiviral.2020.104710","article-title":"The discovery and development of filociclovir for the prevention and treatment of human cytomegalovirus-related disease","volume":"176","author":"Hussein","year":"2020","journal-title":"Antiviral. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e00717","DOI":"10.1128\/AAC.00717-19","article-title":"Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers","volume":"63","author":"Rouphael","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s11899-020-00557-6","article-title":"Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy","volume":"15","author":"Hakki","year":"2020","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6877","DOI":"10.1523\/JNEUROSCI.0970-17.2017","article-title":"Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities","volume":"37","author":"Ornaghi","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.virol.2016.09.012","article-title":"Mood stabilizers inhibit cytomegalovirus infection","volume":"499","author":"Ornaghi","year":"2016","journal-title":"Virology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.antiviral.2018.07.013","article-title":"Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus","volume":"157","author":"Chou","year":"2018","journal-title":"Antiviral. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105062","DOI":"10.1016\/j.antiviral.2021.105062","article-title":"The antifungal drug isavuconazole inhibits the replication of human cytomegalovirus (HCMV) and acts synergistically with anti-HCMV drugs","volume":"189","author":"Mercorelli","year":"2021","journal-title":"Antiviral. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.jcv.2005.09.021","article-title":"Is combination antiviral therapy for CMV superior to monotherapy?","volume":"35","year":"2006","journal-title":"J. Clin. Virol."},{"key":"ref_92","first-page":"96","article-title":"Compassionate use of letermovir in a 2-year-old immunocompromised child with resistant cytomegalovirus disease","volume":"9","author":"Decosterd","year":"2020","journal-title":"J. Pediatric. Infect. Dis. Soc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.bbmt.2020.01.027","article-title":"Letermovir for secondary prophylaxis of cytomegalovirus infection and disease after allogeneic hematopoietic cell transplantation: Results from the French compassionate program","volume":"26","author":"Robin","year":"2020","journal-title":"Biol. Blood Marrow. Transplant."},{"key":"ref_94","unstructured":"(2022, November 28). US FDA Website, Available online: https:\/\/www.fda.gov\/news-events\/public-health-focus\/expanded-access."},{"key":"ref_95","unstructured":"(2021, January 01). EMA Website. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory\/research-development\/compassionate-use."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1080\/14712598.2021.1857720","article-title":"Cell therapy for cytomegalovirus infection","volume":"21","author":"Neill","year":"2021","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.jtct.2021.09.010","article-title":"American Society for Transplantation and Cellular Therapy Series: #4-Cytomegalovirus treatment and management of resistant or refractory infections after hematopoietic cell transplantation","volume":"27","author":"Yong","year":"2021","journal-title":"Transplant. Cell Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1182\/blood.2020009396","article-title":"Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation","volume":"138","author":"Zamora","year":"2021","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e0126421","DOI":"10.1128\/JVI.01264-21","article-title":"A Live Olfactory Mouse Cytomegalovirus Vaccine, Attenuated for Systemic Spread, Protects against Superinfection","volume":"95","author":"Farrell","year":"2021","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"eabm2536","DOI":"10.1126\/sciadv.abm2536","article-title":"Structural basis for HCMV Pentamer receptor recognition and antibody neutralization","volume":"8","author":"Kschonsak","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_101","first-page":"1","article-title":"Human cytomegalovirus (HCMV) infection\/re-infection: Development of a protective HCMV vaccine","volume":"42","author":"Gerna","year":"2019","journal-title":"New Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Ligat, G., Alain, S., and Hantz, S. (2021). Towards a Prophylactic Vaccine for the Prevention of HCMV Infection. Vaccines, 9.","DOI":"10.3390\/vaccines9090968"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Scarpini, S., Morigi, F., Betti, L., Dondi, A., Biagi, C., and Lanari, M. (2021). Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice. Vaccines, 9.","DOI":"10.3390\/vaccines9060551"},{"key":"ref_104","unstructured":"(2020, August 18). Cytomegalovirus (CMV) and Congenital CMV Infection\u2013CDC, Available online: https:\/\/www.cdc.gov\/cmv\/index.html."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e2034","DOI":"10.1002\/rmv.2034","article-title":"Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis","volume":"29","author":"Zuhair","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1017\/S0950268817000103","article-title":"Seroprevalence of cytomegalovirus infection in France in 2010","volume":"145","author":"Antona","year":"2017","journal-title":"Epidemiol. Infect."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1086\/508173","article-title":"Seroprevalence of cytomegalovirus infection in the United States, 1988-1994","volume":"43","author":"Staras","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Lachmann, R., Loenenbach, A., Waterboer, T., Brenner, N., Pawlita, M., Michel, A., Thamm, M., Poethko-M\u00fcller, C., Wichmann, O., and Wiese-Posselt, M. (2018). Cytomegalovirus (CMV) seroprevalence in the adult population of Germany. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200267"},{"key":"ref_109","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."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/7\/12\/439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:22Z","timestamp":1760146882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/7\/12\/439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":109,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["tropicalmed7120439"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed7120439","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}