{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:05:41Z","timestamp":1784178341983,"version":"3.55.0"},"reference-count":107,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["2026300391"],"award-info":[{"award-number":["2026300391"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Human viral entry receptor mouse models exist to overcome a fundamental experimental barrier: many clinically important viruses bind their human entry factors far more efficiently than the corresponding murine orthologs, leaving conventional mice unable to support authentic infection, physiological tissue tropism, or meaningful countermeasure evaluation. This review is organized around the receptor-humanization concept rather than around a single coronavirus model. Engineering strategies compared here include random transgenesis, endogenous-locus knock-in, minimal receptor-interface humanization, conditional and inducible expression, and transient vector-mediated delivery. Receptor systems covered span human angiotensin-converting enzyme 2 (hACE2)-dependent sarbecoviruses, human dipeptidyl peptidase 4 (hDPP4)-dependent Middle East respiratory syndrome coronavirus (MERS-CoV), human cluster of differentiation 4\/human C-C chemokine receptor type 5 (hCD4\/hCCR5)-dependentt human immunodeficiency virus type 1 (HIV-1), adenovirus receptor models, human intercellular adhesion molecule 1 (hICAM-1) rhinovirus systems, hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis D virus (HDV) entry-factor models, measles receptor models, poliovirus receptor\/CD155 (PVR\/CD155) models, human scavenger receptor class B member 2 (hSCARB2) enterovirus systems, and human transferrin receptor 1 (hTfR1) arenavirus models. We then discuss how these platforms support antibody evaluation, Fc-effector analysis, vaccine protection, variant benchmarking, and safety assessment. These models yield the most reliable data when the experimental question is explicitly entry-dependent and when receptor expression level, anatomical distribution, pathology window, and immune context have all been independently validated. They are least informative when receptor expression is non-physiological, when disease readouts are driven by promoter artifacts, or when post-entry species barriers remain the dominant bottleneck. A validation-centered framework is therefore proposed to guide the selection of each model for the specific antiviral antibody or vaccine question it can legitimately answer.<\/jats:p>","DOI":"10.3390\/vaccines14070614","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:12:53Z","timestamp":1784023973000},"page":"614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Human Viral Entry Receptor Mouse Models in Advancing Antiviral Antibodies and Vaccines"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-9274","authenticated-orcid":false,"given":"Na","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9158-8641","authenticated-orcid":false,"given":"Rameez","family":"Ishaq","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deshan","family":"Ren","sequence":"additional","affiliation":[{"name":"National Resource Center for Mutant Mice and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing 210061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Hu","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Masemann, D., Ludwig, S., and Planz, O. 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