{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:58:54Z","timestamp":1791388734212,"version":"4.3.3"},"reference-count":97,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002703","name":"University-Level Talent Start-up Project of Jiangsu University","doi-asserted-by":"publisher","award":["5501280006"],"award-info":[{"award-number":["5501280006"]}],"id":[{"id":"10.13039\/501100002703","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Enteroviruses (EVs), particularly those within the species Enterovirus A and B, represent a significant global public health burden, especially in infants and young children. While often causing self-limiting hand, foot, and mouth disease (HFMD), certain serotypes can lead to severe neurological and cardiopulmonary complications. This comprehensive review focuses on the major pathogenic serotypes, including enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), coxsackievirus A6 (CV-A6), coxsackievirus B3 (CV-B3), and enterovirus D68 (EV-D68). We began by reconstructing a phylogenetic tree based on VP1 protein sequences, elucidating the genetic relationships and evolutionary patterns among these serotypes, which underpin their diverse antigenicity and epidemiology. Building upon this genetic foundation, the review then provides a detailed synthesis of their distinct pathogenesis, highlighting the five-phase clinical progression from exanthematous phase to convalescence, and their unique tropisms for target organs such as the central nervous system and heart. Progressing to the molecular mechanisms, a critical component of this work is a systematic summary of the specific host receptors that mediate viral entry, including SCARB2 for EV-A71 and CV-A16, sialic acid and ICAM-5 for EV-D68, and CAR\/CD55 for CV-B3, explaining the mechanistic basis for their tissue specificity and pathogenicity. Finally, to translate these insights into clinical applications, we critically evaluate the current landscape of vaccine development, noting the high efficacy (~90%) of inactivated EV-A71 vaccines in Asia and the significant global success of poliovirus vaccines, while also addressing the stark lack of cross-protective or licensed vaccines for other prevalent serotypes like CV-A16, CV-A6, and EV-D68. The review concludes that the high genetic diversity and serotype-specific immunity of enteroviruses pose a major challenge, necessitating a concerted shift towards the development of broad-spectrum vaccines and therapeutics informed by an integrated understanding of viral evolution, receptor usage, and pathogenesis.<\/jats:p>","DOI":"10.3390\/cells14201617","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T10:28:36Z","timestamp":1760696916000},"page":"1617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Pathogenesis and Virulence of the Major Enterovirus Pathogens Associated with Severe Clinical Manifestations: A Comprehensive Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-2926","authenticated-orcid":false,"given":"Yuwei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiheliya","family":"Maisimu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihang","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suling","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, Y., Li, H., Huang, X., Huang, Y., Lv, M., Tang, H., Han, X., Liu, J., Liang, Y., and Zang, G. (2025). NAD+ Suppresses EV-D68 Infection by Enhancing Anti-Viral Effect of SIRT1. Viruses, 17.","DOI":"10.3390\/v17020175"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2361","DOI":"10.1002\/rmv.2361","article-title":"Insight into the Enterovirus A71: A review","volume":"32","author":"Kinobe","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.3855\/jidc.18411","article-title":"Molecular characteristics of the structure protein VP1 in Coxsackievirus A10 Isolates from China","volume":"18","author":"Wang","year":"2024","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gaume, L., Chabrolles, H., Bisseux, M., Lopez-Coqueiro, I., Dehouck, L., Mirand, A., Henquell, C., Gosselet, F., Archimbaud, C., and Bailly, J.L. (2024). Enterovirus A71 crosses a human blood-brain barrier model through infected immune cells. Microbiol. Spectr., 12.","DOI":"10.1128\/spectrum.00690-24"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Waghchaure, R., Kunjumon, J., Ashraf, A.F., Raju, R.M., Shete, A., Cherian, S., and Lavania, M. (2025). Complete-Genome Analysis of Echovirus-30 Isolated from an Encephalitis Case in India Revealed Distinct Mutations. Microorganisms, 13.","DOI":"10.3390\/microorganisms13071580"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, X., Zhang, Y., Li, H., Zheng, H., Wang, J., Liao, Y., Yu, L., Li, D., and Zhao, H. (2025). The Expression Pattern of the Splice Variants of Coxsackievirus and Adenovirus Receptor Impacts CV-B3-Induced Encephalitis and Myocarditis in Neonatal Mice. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157163"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1097\/00126334-200010001-00004","article-title":"Cocaine injection and coxsackievirus B3 infection increase heart disease during murine AIDS","volume":"25","author":"Jiang","year":"2000","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100851","DOI":"10.1016\/j.epidem.2025.100851","article-title":"Transmission dynamics of Norovirus GII and Enterovirus in Switzerland during the COVID-19 pandemic (2021\u20132022) as evidenced in wastewater","volume":"52","author":"Huisman","year":"2025","journal-title":"Epidemics"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhang, X., Sun, R., Hou, J., Jia, W., Li, P., Shi, S., Song, C., and Cheng, Y. (2025). Clinical characteristics of fatal cases of hand, foot and mouth disease in children. Front. Pediatr., 13.","DOI":"10.3389\/fped.2025.1522164"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.ijmmb.2022.04.005","article-title":"Changing epidemiology of human enteroviruses (HEV) in a hand, foot and mouth disease outbreak in Vellore, south India","volume":"40","author":"George","year":"2022","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5569829","DOI":"10.1155\/crpe\/5569829","article-title":"Clinical Presentation and Outcome of Five Neonates With Enterovirus Central Nervous System Infection: Contrasting One Kawasaki-Like Case With Cardiac Involvement and Seizures With Four Benign Cases","volume":"2025","author":"Peternell","year":"2025","journal-title":"Case Rep. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lizasoain, A., Mart\u00ednez, N., de Mora, C., Rodr\u00edguez, E., Ledezma, N., and Colina, R. (2024). Identification of the Emerging C1-like Lineage of Enterovirus A71 in Two Uruguayan Children with Hand-Foot-and-Mouth Disease and Neurological Complications. Viruses, 16.","DOI":"10.3390\/v16111752"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jcrc.2006.02.005","article-title":"Heart rate variability monitoring in the detection of central nervous system complications in children with enterovirus infection","volume":"21","author":"Lin","year":"2006","journal-title":"J. Crit. Care"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hu, Y.L., Cheng, A.L., Chen, S.H., Fang, C.T., and Chang, L.Y. (J. Formos. Med. Assoc. = Taiwan Yi Zhi, 2024). Febrile young infants and the association with enterovirus infection, J. Formos. Med. Assoc. = Taiwan Yi Zhi, Online ahead of print.","DOI":"10.1016\/j.jfma.2024.09.025"},{"key":"ref_15","first-page":"e15625","article-title":"A Case Report of Acute Flaccid Paralysis Caused by Enterovirus D68 Infection: The Beginning of a Polio-Like Epidemic?","volume":"13","author":"Nafisa","year":"2021","journal-title":"Cureus"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/jmv.23184","article-title":"Sabin and wild polioviruses from apparently healthy primary school children in northeastern Nigeria","volume":"84","author":"Baba","year":"2012","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Phyu, W.K., Ong, K.C., and Wong, K.T. (2016). A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147463"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1016\/j.watres.2007.06.002","article-title":"Molecular quantitative analysis of human viruses in California stormwater","volume":"41","author":"Rajal","year":"2007","journal-title":"Water Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fu, L., Zhang, X.Y., Jin, W.P., Wang, C., Qian, S.S., Wang, M.J., Wang, W.H., Meng, S.L., Guo, J., and Wang, Z.J. (2023). Identification of a Conserved, Linear Epitope on VP3 of Enterovirus A Species Recognized by a Broad-Spectrum Monoclonal Antibody. Viruses, 15.","DOI":"10.3390\/v15041028"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Helgers, L.C., Bhoekhan, M.S., Pajkrt, D., Wolthers, K.C., Geijtenbeek, T.B.H., and Sridhar, A. (2022). Human Dendritic Cells Transmit Enterovirus A71 via Heparan Sulfates to Target Cells Independent of Viral Replication. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.02822-22"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1016\/j.vaccine.2021.05.058","article-title":"Preclinical safety assessment of a combined vaccine against Hepatitis a virus and enterovirus 71","volume":"39","author":"Yang","year":"2021","journal-title":"Vaccine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00377-20","DOI":"10.1128\/msphere.00377-20","article-title":"A Mouse Model for Infection with Enterovirus A71 in Small Extracellular Vesicles","volume":"5","author":"Gu","year":"2020","journal-title":"mSphere"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Phyu, W.K., Ong, K.C., Kong, C.K., Alizan, A.K., Ramanujam, T.M., and Wong, K.T. (2017). Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa. Sci. Rep., 7.","DOI":"10.1038\/srep45069"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/ajcp\/aqw089","article-title":"Pathologic Studies of Fatal Encephalomyelitis in Children Caused by Enterovirus 71","volume":"146","author":"Xing","year":"2016","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127276","DOI":"10.1016\/j.vaccine.2025.127276","article-title":"Cellular response, persistent humoral response and efficacy elicited by a CV-A16 vaccine candidate in mice","volume":"61","author":"Qin","year":"2025","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00705-016-3157-4","article-title":"Enterovirus A71 and coxsackievirus A16 show different replication kinetics in human neuronal and non-neuronal cell lines","volume":"162","author":"Yogarajah","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"150","DOI":"10.47665\/tb.38.1.026","article-title":"Detection of enteroviruses during a 2018 hand, foot and mouth disease outbreak in Malaysia","volume":"38","author":"Lee","year":"2021","journal-title":"Trop. Biomed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2087","DOI":"10.1002\/rmv.2087","article-title":"A review and meta-analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand-foot-mouth disease in China and global implications","volume":"30","author":"Zhao","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jcv.2010.02.002","article-title":"Co-circulation of coxsackieviruses A6 and A10 in hand, foot and mouth disease outbreak in Finland","volume":"48","author":"Blomqvist","year":"2010","journal-title":"J. Clin. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1097\/INF.0000000000000120","article-title":"Dermatological spectrum of hand, foot and mouth disease from classical to generalized exanthema","volume":"33","author":"Hubiche","year":"2014","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcv.2018.11.003","article-title":"Severe atypical hand-foot-and-mouth disease in adults due to coxsackievirus A6: Clinical presentation and phylogenesis of CV-A6 strains","volume":"110","author":"Broccolo","year":"2019","journal-title":"J. Clin. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jcv.2018.09.002","article-title":"Molecular epidemiology of coxsackievirus A6 circulating in Hong Kong reveals common neurological manifestations and emergence of novel recombinant groups","volume":"108","author":"Lau","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8881","DOI":"10.1021\/acs.nanolett.3c01983","article-title":"Cytoplasm Hydrogelation-Mediated Cardiomyocyte Sponge Alleviated Coxsackievirus B3 Infection","volume":"23","author":"Wang","year":"2023","journal-title":"Nano Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e70915","DOI":"10.1096\/fj.202500209R","article-title":"A 2B Protein-Derived Peptide Effectively Inhibits Coxsackievirus B3 Infection","volume":"39","author":"Yuan","year":"2025","journal-title":"FASEB J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"121","DOI":"10.33594\/000000125","article-title":"A Kidnapping Story: How Coxsackievirus B3 and Its Host Cell Interact","volume":"53","author":"Peischard","year":"2019","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1128\/JVI.02680-06","article-title":"Molecular determinants of the interaction between coxsackievirus protein 3A and guanine nucleotide exchange factor GBF1","volume":"81","author":"Wessels","year":"2007","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1099\/0022-1317-80-4-921","article-title":"Enterovirus receptors and virus replication in human leukocytes","volume":"80","author":"Vuorinen","year":"1999","journal-title":"J. Gen. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e06688","DOI":"10.1002\/advs.202506688","article-title":"A Novel Class of Multi-substituted Diaryl Scaffold Derivatives Inhibit Glioblastoma Progression by Targeting CD155","volume":"12","author":"Wang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dawson, K.L.D., Seuberlich, T., and Pesavento, P.A. (Vet. Pathol., 2025). Neurotropic enteric viruses in animals: Comparative research, knowledge gaps, and the role of pathology, Vet. Pathol., Online ahead of print.","DOI":"10.1177\/03009858251334347"},{"key":"ref_40","first-page":"899","article-title":"Acute Transverse Myelitis in a Child Following Oral Live Polio Vaccine Administration","volume":"18","author":"Kramarov","year":"2025","journal-title":"Int. Med. Case Rep. J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Grizer, C.S., Messacar, K., and Mattapallil, J.J. (2024). Enterovirus-D68\u2014A Reemerging Non-Polio Enterovirus that Causes Severe Respira-tory and Neurological Disease in Children. Front. Virol., 4.","DOI":"10.3389\/fviro.2024.1328457"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e0052623","DOI":"10.1128\/msphere.00526-23","article-title":"Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection","volume":"9","author":"Laksono","year":"2024","journal-title":"mSphere"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Aguglia, G., Coyne, C.B., Dermody, T.S., Williams, J.V., and Freeman, M.C. (2023). Contemporary enterovirus-D68 isolates infect human spinal cord organoids. mBio, 14.","DOI":"10.1128\/mbio.01058-23"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1021\/acsinfecdis.5c00063","article-title":"Sialic Acid-Containing Glycolipids Extend the Receptor Repertoire of Enterovirus-D68","volume":"11","author":"Montenarie","year":"2025","journal-title":"ACS Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lizasoain, A., Mir, D., Salvo, M., Bortagaray, V., Masachessi, G., Far\u00edas, A., Rodr\u00edguez-Osorio, N., Nates, S., Victoria, M., and Colina, R. (2021). First evidence of enterovirus A71 and echovirus 30 in Uruguay and genetic relationship with strains circulating in the South American region. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255846"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.1093\/infdis\/jiaf179","article-title":"Epidemiological and Clinical Insights into Enterovirus Circulation in Europe, 2018-2023: A Multicenter Retrospective Surveillance Study","volume":"232","author":"Vanhulle","year":"2025","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Vlok, M., and Majer, A. (2025). Global Prevalence of Non-Polio Enteroviruses Pre- and Post COVID-19 Pandemic. Microorganisms, 13.","DOI":"10.3390\/microorganisms13081801"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, T., Sun, Q., Liu, H., Yang, M., Chen, S., Sun, W., Xu, J., Yan, D., Zhu, S., and Han, Z. (2025). Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1634547"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1016\/j.jinf.2013.09.020","article-title":"The enteroviruses: Problems in need of treatments","volume":"68","author":"Abzug","year":"2014","journal-title":"J. Infect."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cevallos, C., Jarmoluk, P., Sviercz, F., Freiberger, R.N., L\u00f3pez, C.A.M., Delpino, M.V., and Quarleri, J. (2025). Ferroptosis and mitochondrial ROS are central to SARS-CoV-2-induced hepatocyte death. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1625928"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"107221","DOI":"10.1016\/j.ijantimicag.2024.107221","article-title":"Bacteriophage-resistant carbapenem-resistant Klebsiella pneumoniae shows reduced antibiotic resistance and virulence","volume":"64","author":"Chen","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Zu, S., Zhang, Y., Zhao, F., Jin, X., and Hu, H. (2021). Porcine Deltacoronavirus Utilizes Sialic Acid as an Attachment Receptor and Trypsin Can Influence the Binding Activity. Viruses, 13.","DOI":"10.3390\/v13122442"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s41422-023-00917-w","article-title":"LDLR is an entry receptor for Crimean-Congo hemorrhagic fever virus","volume":"34","author":"Xu","year":"2024","journal-title":"Cell Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hamidi, M., Ong, K.C., Tan, S.H., and Wong, K.T. (2025). An Intracerebrally-Infected Mouse Model of Enterovirus A71 Demonstrates Restricted Inter-Neuronal Spread Within the Brain Parenchyma Despite Strong SCARB2 Expression. Neuropathol. Appl. Neurobiol., 51.","DOI":"10.1111\/nan.70031"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, W.G., Wang, X., Li, N., Kuang, D.X., Tong, P.F., Lu, C.X., Han, Y.Y., Sun, X.M., Dai, J.J., and Liu, L.D. (2025). EV-A71 invades the central nervous system and affects the blood-brain barrier in a tree shrew model. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1583768"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12985-024-02461-4","article-title":"Correlations of PSGL-1 VNTR polymorphism with the susceptibility to severe HFMD associated with EV-71 and the immune status after infection","volume":"21","author":"Wang","year":"2024","journal-title":"Virol. J."},{"key":"ref_57","first-page":"97","article-title":"Expression of EV71-VP1, PSGL-1 and SCARB2 in Tissues of Infants with Brain Stem Encephalitis","volume":"31","author":"Li","year":"2015","journal-title":"Fa Yi Xue Za Zhi"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1743-422X-6-141","article-title":"Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells","volume":"6","author":"Yang","year":"2009","journal-title":"Virol. J."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ke, X., Zhang, Y., Liu, Y., Miao, Y., Zheng, C., Luo, D., Sun, J., Hu, Q., Xu, Y., and Wang, H. (2020). A Single Mutation in the VP1 Gene of Enterovirus 71 Enhances Viral Binding to Heparan Sulfate and Impairs Viral Pathogenicity in Mice. Viruses, 12.","DOI":"10.3390\/v12080883"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.00681-18","article-title":"Amino Acid Variation at VP1-145 of Enterovirus 71 Determines Attachment Receptor Usage and Neurovirulence in Human Scavenger Receptor B2 Transgenic Mice","volume":"92","author":"Kobayashi","year":"2018","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.bbrc.2013.03.044","article-title":"Beta-actin variant is necessary for Enterovirus 71 replication","volume":"433","author":"Lui","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Too, I.H.K., Bonne, I., Tan, E.L., Chu, J.J.H., and Alonso, S. (2018). Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006778"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Su, W., Huang, S., Zhu, H., Zhang, B., and Wu, X. (2020). Interaction between PHB2 and Enterovirus A71 VP1 Induces Autophagy and Affects EV-A71 Infection. Viruses, 12.","DOI":"10.3390\/v12040414"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.02251-17","article-title":"Fibronectin Facilitates Enterovirus 71 Infection by Mediating Viral Entry","volume":"92","author":"He","year":"2018","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s13365-019-00800-8","article-title":"Enterovirus A71 capsid protein VP1 increases blood-brain barrier permeability and virus receptor vimentin on the brain endothelial cells","volume":"26","author":"Wang","year":"2020","journal-title":"J. Neurovirol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Sridhar, A., Depla, J.A., Mulder, L.A., Karelehto, E., Brouwer, L., Kruiswijk, L., Vieira de S\u00e1, R., Meijer, A., Evers, M.M., and van Kuppeveld, F.J.M. (2022). Enterovirus D68 Infection in Human Primary Airway and Brain Organoids: No Additional Role for Heparan Sulfate Binding for Neurotropism. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.01694-22"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.00578-19","article-title":"Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid","volume":"93","author":"Hixon","year":"2019","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.chom.2016.09.013","article-title":"ICAM-5\/Telencephalin Is a Functional Entry Receptor for Enterovirus D68","volume":"20","author":"Wei","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1038\/s41467-019-11256-z","article-title":"Bypassing pan-enterovirus host factor PLA2G16","volume":"10","author":"Baggen","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"26418","DOI":"10.1074\/jbc.M111.251140","article-title":"Sulfated glycosaminoglycans are required for specific and sensitive fibroblast growth factor (FGF) 19 signaling via FGF receptor 4 and betaKlotho","volume":"286","author":"Nakamura","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1038\/s41586-025-08908-0","article-title":"MFSD6 is an entry receptor for enterovirus D68","volume":"641","author":"Varanese","year":"2025","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Li, Z., Li, H., Liu, X., Zhou, J., Gao, D., Yang, W., Xia, H., Dou, C., Yu, Z., and Guo, H. (2025). Characterisation of a secreted MFSD6-Fc microbody as a decoy receptor for respiratory enterovirus D68. eBioMedicine, 120.","DOI":"10.1016\/j.ebiom.2025.105915"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.chom.2024.12.015","article-title":"MFSD6 is an entry receptor for respiratory enterovirus D68","volume":"33","author":"Liu","year":"2025","journal-title":"Cell Host Microbe"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Guo, X., Zeng, S., Ji, X., Meng, X., Lei, N., Yang, H., and Mu, X. (2022). Type I Interferon-Induced TMEM106A Blocks Attachment of EV-A71 Virus by Interacting With the Membrane Protein SCARB2. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.817835"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e2118590119","DOI":"10.1073\/pnas.2118590119","article-title":"Molecular basis of differential receptor usage for naturally occurring CD55-binding and -nonbinding coxsackievirus B3 strains","volume":"119","author":"Wang","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10547","DOI":"10.1038\/s41467-024-55043-x","article-title":"Coxsackievirus and adenovirus receptor expression facilitates enteroviral infections to drive the development of pancreatic cancer","volume":"15","author":"Bastea","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1038\/s41418-025-01496-6","article-title":"Targeting the poliovirus receptor to activate T cells and induce myeloid-derived suppressor cells to differentiate to pro-inflammatory macrophages via the IFN-\u03b3-p-STAT1-IRF8 axis in cancer therapy","volume":"2","author":"Feng","year":"2025","journal-title":"Cell Death Differ."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/infdis\/jiw502","article-title":"2-Year Efficacy, Immunogenicity, and Safety of Vigoo Enterovirus 71 Vaccine in Healthy Chinese Children: A Randomized Open-Label Study","volume":"215","author":"Wei","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.4161\/hv.24949","article-title":"Progress on the research and development of inactivated EV71 whole-virus vaccines","volume":"9","author":"Liang","year":"2013","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"eadi1625","DOI":"10.1126\/scitranslmed.adi1625","article-title":"A self-amplifying RNA vaccine prevents enterovirus D68 infection and disease in preclin-ical models","volume":"16","author":"Warner","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Cheng, J., Krug, P.W., Lei, H., Moss, D.L., Lang, Z.C., Morton, A.J., Shen, C.-H., Pletnev, S., Huang, R.K., and Pierson, T.C. (2025). Structural insights from vaccine candidates for EV-D68. Commun. Biol., 8.","DOI":"10.1038\/s42003-025-08253-y"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Tan, X.H., Chong, W.L., Lee, V.S., Abdullah, S., Jasni, K., Suarni, S.Q., Perera, D., Sam, I.C., and Chan, Y.F. (2023). Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71. Vaccines, 11.","DOI":"10.20944\/preprints202307.0846.v1"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1080\/22221751.2020.1823889","article-title":"Immune responses of a CV-A16 live attenuated candidate strain and its protective effects in rhesus monkeys","volume":"9","author":"Yang","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_84","first-page":"1779","article-title":"Immunogenicity of trivalent DNA vaccine candidate encapsulated in Chitosan-TPP nanoparticles against EV-A71 and CV-A16","volume":"19","author":"Yew","year":"2024","journal-title":"Nanomedicine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1007\/s00705-019-04418-3","article-title":"Intranasal immunization with coxsackievirus A16 virus-like particles confers protection against lethal infection in neonatal mice","volume":"164","author":"Chen","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1038\/emi.2016.73","article-title":"EV-A71 vaccine licensure: A first step for multivalent enterovirus vaccine to control HFMD and other severe diseases","volume":"5","author":"Mao","year":"2016","journal-title":"Emerg. Microbes Infect."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Godin, A., Brickley, E.B., Connor, R.I., Wieland-Alter, W.F., Weiner, J.A., Ackerman, M.E., Modlin, J.F., Sajjad, O.M., Arita, M., and Gast, C. (2025). Intestinal mucosal immune responses to novel oral poliovirus vaccine type 2 in healthy newborns. Clin. Infect. Dis., ciaf484.","DOI":"10.1093\/cid\/ciaf484"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"MacLeod, D.A., Tobin, J.K., Bushnell, R.V., Wiggins, T.J., Ts, S., Nadipelly, R., Lawson, S., Pillai, V.V., Tobin, G.J., and Dollery, S.J. (2025). Immune and Safety Analysis of ultraIPV(TM), a Novel UVC-Inactivated Polio Vaccine. Viruses, 17.","DOI":"10.3390\/v17070915"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Liang, J., Zhang, Q., Li, Y., and Wang, L. (2025). Advances and challenges in poliomyelitis vaccines: A comprehensive review of development, production, and global deployment. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1611028"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s41182-025-00722-8","article-title":"Global partnerships in combating tropical diseases: Assessing the impact of a U.S. withdrawal from the WHO","volume":"53","author":"Ogieuhi","year":"2025","journal-title":"Trop. Med. Health"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2500605","DOI":"10.2807\/1560-7917.ES.2025.30.34.2500605","article-title":"Early detection of a circulating pre-vaccine-derived poliovirus type 1 (pre-VDPV1) variant linked to an acute flaccid polio case prior to VDPV1 emergence, Israel, 2024 to 2025","volume":"30","author":"Zuckerman","year":"2025","journal-title":"Euro Surveill."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Mercer, L.D., Se\u00f1a, A.C., Colgate, E.R., Crothers, J.W., Wright, P.F., Al-Ibrahim, M., Tritama, E., Vincent, A., Mainou, B.A., and Zhang, Y. (Lancet Infect. Dis., 2025). Safety and immunogenicity of novel live attenuated type 1 and type 3 oral poliomyelitis vaccines in healthy adults in the USA: A first-in-human, observer-masked, multicentre, phase 1 randomised controlled trial, Lancet Infect. Dis., Online ahead of print.","DOI":"10.1016\/S1473-3099(25)00285-3"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"199486","DOI":"10.1016\/j.virusres.2024.199486","article-title":"Advances in human norovirus research: Vaccines, genotype distribution and antiviral strategies","volume":"350","author":"Chen","year":"2024","journal-title":"Virus Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Seo, S.H., Choi, J.A., Yang, E., Park, H., Jung, D.I., Kim, J.O., Yang, J.S., and Song, M. (2025). Mouse strain-dependent neutralizing antibody responses to Zika virus vaccines. J. Microbiol., 63.","DOI":"10.71150\/jm.2504005"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Thornhill-Wadolowski, E., Ruter, D.L., Yan, F., Gajera, M., Kurt, E., Samanta, L., Leigh, K., Zhu, J., Guo, Z., and Wang, Z. (2025). Development of an Influenza\/COVID-19 Combination mRNA Vaccine Containing a Novel Multivalent Antigen Design That Enhances Immunogenicity of Influenza Virus B Hemagglutinins. Vaccines, 13.","DOI":"10.3390\/vaccines13060628"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"100088","DOI":"10.1016\/j.ccmp.2023.100088","article-title":"The Anti-parasitic Effect of Extract of Ceiba pentandra (L.) Gaertn Is Related to Its Anti-inflammatory, Analgesic and Anthelmintic Activities on Haemonchus contortus","volume":"3","author":"Calvin","year":"2023","journal-title":"Clin. Complement. Med. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"200194","DOI":"10.1016\/j.ctmp.2025.200194","article-title":"Ceropegia variegata: Phytochemical profiling, antioxidant prowess, and antimicrobial potential","volume":"6","author":"Saeed","year":"2025","journal-title":"Clin. Tradit. Med. Pharmacol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/20\/1617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T10:48:00Z","timestamp":1760698080000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/20\/1617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":97,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["cells14201617"],"URL":"https:\/\/doi.org\/10.3390\/cells14201617","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]}}}