Application of the humanized mouse model in research into SARS-CoV-2 infection (Review)

Xiaoyue Feng; Yadong Wang; Yuan Li; Jinzhao Long; Fang Liu; Haiyan Yang

Xiaoyue Feng, Yadong Wang, Yuan Li, Jinzhao Long, Fang Liu, Professor Haiyan Yang

Medicine International, doi:10.3892/mi.2025.293

the coronavirus disease 2019 pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SarS-CoV-2) has had a profound impact on global public health. the complexity of its pathogenic mechanisms and host interactions urgently requires high-fidelity animal models to support research. Humanized mouse models break the species barrier through gene editing and immune reconstitution technologies, providing a key tool to simulate human infection characteristics and pathological processes. a number of studies have reported the application of humanized mouse models in the fields of COVID-19 research, such as SarS-CoV-2 pathogenesis, anti-SarS-CoV-2 drug discovery and vaccine development, etc. the present review aimed to systematically document the latest advances in the application of humanized mouse models based on different construction strategies, such as receptor humanization, immune system humanization and composite humanization. these models have not only elucidated the pathogenicity differences and immune escape mechanisms of SarS-CoV-2 variants, but have also validated the efficacy of broad-spectrum anti-SARS-CoV-2 strategies, including angiotensin-converting enzyme 2-targeted therapies, antibody cocktail regimens and mucosal vaccines. additionally, humanized mouse models have played a pivotal role in investigating the mechanisms underlying long CoVID. By revealing the multi-system pathogenic mechanisms of pulmonary fibrosis, neurodegeneration and intestinal microbiota dysregulation, these models provide a theoretical foundation for the development of targeted intervention strategies. Contents 1. Introduction 2. Strategies for the construction of humanized mouse models 3. application of the humanized mouse model in research into SarS-CoV-2 infection 4. limitations 5. Conclusions

Authors' contributions HY conceptualized the study. XF, YW, Yl, Jl and Fl performed the literature search. XF wrote the manuscript. all authors have read and approved the final manuscript. Data authentication is not applicable. Ethics approval and consent to participate Not applicable. Patient consent for publication Not applicable. Competing interests the authors declare that they have no competing interests.

References

Adams Le, Dinnon, Iii, Hou, Sheahan Tp et al., Critical aCE2 determinants of SarS-CoV-2 and group 2B coronavirus infection and replication, mBio

Bello-Perez, Hurtado-Tamayo, Az, Lamers, Requena-Platek R et al., SarS-CoV-2 orF8 accessory protein is a virulence factor, mBio

Botella-Asunción, Rivero-Buceta, Vidaurre-Agut, Rey-Campos, Moreno A, Mendoza L et al., aG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity, Biomed Pharmacother

Brumeanu Td, Vir, Karim Af, Kar, Benetiene et al., Human-immune-system (HIS) humanized mouse model (DRAGA: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for CoVID-19, Hum Vaccin Immunother

Brumeanu Td, Vir, Karim Af, Kar, Benetiene et al., a Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for CoVID

Bruter Av, Korshunova, Kubekina, Sergiev, Kalinina Aa et al., Novel transgenic mice with Cre-dependent co-expression of GFP and human aCE2: a safe tool for study of CoVID-19 pathogenesis, transgenic res

Buchholz, Szigety, Imbiakha, Gao, Frankfurter et al., Cell-autonomous requirement for aCE2 across organs in lethal mouse SarS-CoV-2 infection, PloS Biol

Cao, St, Huang, Wang, Ml et al., Mast cell degranulationtriggered by SarS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury, Virol Sin

Casasnovas, Margolles, Ma, Guzmán, Melero R et al., Nanobodies protecting from lethal SarS-CoV-2 infection target receptor binding epitopes preserved in virus variants other than omicron, Front Immunol

Chan, Guo, Chan, Tang, Cai et al., Identification of novel smallmolecule inhibitors of SarS-CoV-2 by chemical genetics, acta Pharm Sin B

Chi, Cheng, Zheng, Zhang, Zhao et al., An engineered IgG-VHH bispecific antibody against SarS-CoV-2 and its variants, Small Methods

Choi, Gadhave, Villano, Pekosz, Mao et al., Generation and characterization of a humanized aCE2 mouse model to study long-term impacts of SarS-CoV-2 infection, J Med Virol

Chuang, Hsueh, Hsu, Huang Rh, Tsai et al., SarS-CoV-2 spike protein enhances MaP4K3/GlK-induced aCE2 stability in CoVID-19, EMBo Mol Med

Corti, Purcell, Snell, Veesler, tackling CoVID-19 with neutralizing monoclonal antibodies, Cell

Cui L, Fang, Souza, Guan, Li et al., Innate immune cell activation causes lung fibrosis in a humanized model of long COVID, Proc Natl acad Sci

Da Silva-Santos, Pagni Rl, Gamon, Mlg, De Oliveira Dbl et al., angiotensin-converting enzyme inhibition and/or angiotensin receptor blockade modulate cytokine profiles and improve clinical outcomes in experimental CoVID-19 infection, Int J Mol Sci

De Campos-Mata L, Trinité, Modrego, Vaquero, Pradenas, Pons-Grífols A, Rodrigo Melero et al., a monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SarS-CoV-2 activity, Nat Commun

Deshpande, Lange Kr, Stone, Yohn, Schlesinger et al., The influence of SarS-CoV-2 infection on expression of drug-metabolizing enzymes and transporters in a haCE2 murine model, Pharmacol res Perspect

Di, Lew, Goncin, Ss, Bet et al., SarS-CoV-2 variant-specific infectivity and immune profiles Are detectable in a humanized lung mouse model, Viruses

Dong, Wang, Zhang, Mead, Sa et al., FXa cleaves the SarS-CoV-2 spike protein and blocks cell entry to protect against infection with inferior effects in B.1.1.7 variant

Dos Ramos Almeida Cjl, Veras, Paiva, Schneider, Da et al., Neutrophil virucidal activity against SarS-CoV-2 is mediated by neutrophil extracellular traps, J Infect Dis

Du, Shi R, Zhang, Duan, Zhang et al., a broadly neutralizing humanized aCE2-targeting antibody against SarS-CoV-2 variants, Nat Commun

Frasson, Diamante L, Zangrossi, Carbognin, Pietà et al., Identification of druggable host dependency factors shared by multiple SarS-CoV-2 variants of concern, J Mol Cell Biol

Freitag Tl, Fagerlund R, Nl, Vm, Ugurlu et al., Intranasal administration of adenoviral vaccines expressing SarS-CoV-2 spike protein improves vaccine immunity in mouse models, Vaccine

Fu, Wang, Yuan L, Lin, Huang, Cai et al., a SCID mouse-human lung xenograft model of SarS-CoV-2 infection, theranostics

Fu, Zhang, Wang, Zhang, Hu et al., Structural basis for SarS-CoV-2 neutralizing antibodies with novel binding epitopes, PloS Biol

Gallolu Kankanamalage, Dong, Huang, Spadoni, Wang et al., First-in-class trispecific VHH-Fc based antibody with potent prophylactic and therapeutic efficacy against SARS-CoV-2 and variants, Sci rep

García-Arriaza, Garaigorta, Pérez, Lázaro-Frías A, Zamora et al., CoVID-19 vaccine candidates based on modified vaccinia virus Ankara expressing the SarS-CoV-2 spike induce robust t-and B-cell immune responses and full efficacy in mice, J Virol

García-Ayllón, Ms, Moreno-Pérez O, García-Arriaza, Cortés-Gómez et al., Plasma aCE2 species are differentially altered in CoVID-19 patients, FaSEB J

Ge, Salem Ar, Elsharkawy, Natekar, Guglani et al., Development and characterization of a fully humanized aCE2 mouse model, BMC Biol

Geng, Yuan, Wang, Wang, Qin et al., CD147 antibody specifically and effectively inhibits infection and cytokine storm of SarS-CoV-2 and its variants delta, alpha, beta, and gamma, Signal transduct target ther

Godot, Cardinaud, Galhaut, Coleon, Zurawski et al., targeting SarS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques, Nat Commun

Gu, Chen, Meng, Liu, Xu et al., Spike-based adenovirus vectored CoVID-19 vaccine does not aggravate heart damage after ischemic injury in mice, Commun Biol

Hansen, Baum, Pascal, Russo, Giordano et al., Studies in humanized mice and convalescent humans yield a SarS-CoV-2 antibody cocktail, Science

Haoyu, Jiaoyang, Guangliang, Haofeng L, Pan, Xiongzhi et al., Premature aging effects on CoVID-19 pathogenesis: New insights from mouse models, Sci rep

Heath, Hermanns, Coucha, Burnett, Coucha et al., SARS-CoV-2 spike protein intensifies cerebrovascular complications in diabetic haCE2 Mice through raaS and tlr signaling activation, transl Stroke res

Hoffmann, Kleine-Weber, Schroeder, Krüger, Herrler T, Erichsen et al., SarS-CoV-2 cell entry depends on aCE2 and tMPrSS2 and is blocked by a clinically proven protease inhibitor, Cell

Huang, Wang, Li, Zhao, Hu et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, lancet

Hwang, Kim, Moon, Park, Kim et al., Conversion of host cell receptor into virus destructor by immunodisc to neutralize diverse SarS-CoV-2 variants, adv Healthc Mater

Ikemura, Inaba, Motooka, Katoh, Kirita et al., an engineered aCE2 decoy neutralizes the SarS-CoV-2 omicron variant and confers protection against infection in vivo, Sci transl Med

Jarnagin, Shresta, Dr, animal models for SarS-Cov2/Covid19 research-a commentary, Biochem Pharmacol

Kancagi, Yurtsever, Karakus, Ozer, Cakirsoy et al., Gamma-irradiated SarS-CoV-2 vaccine candidate, oZG-38.61.3, confers protection from SarS-CoV-2 challenge in human aCEIItransgenic mice, Sci rep

Kenney, Montanaro, Hekman, Berneshawi Ar, Cafiero et al., Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SarS-CoV-2 infection, Cell rep

Kita, Moriyama, Sato A, Nomura T, Sakakibara, Inoue, a SarS-CoV-2 antibody broadly neutralizes SarS-related coronaviruses and variants by coordinated recognition of a virusvulnerable site, Immunity

Klein, Wood, Jr, Dhodapkar, Jr et al., Distinguishing features of long CoVID identified through immune profiling, Nature

Lamers, Van Der Vaart, Knoops, Breugem Ti, Mykytyn Az, Beumer et al., Using ex vivo bioengineered lungs to model pathologies and screening therapeutics: a proof-of-concept study, Biotechnol Bioeng

Le Chevalier, Chardenoux, Bourgine, Vesin, Cussigh et al., Mice humanized for MHC and haCE2 with high permissiveness to SarS-CoV-2 omicron replication, Microbes Infect

Li, Han, Hu R, Sun, Li et al., transcriptomic profiling reveals SarS-CoV-2-infected humanized MHC mice recapitulate human post vaccination immune responses, Front Cell Infect Microbiol

Li, Verma, Ortiz, Hawkins, Schnicker et al., adaptation of SarS-CoV-2 to aCE2 H353K mice reveals new spike residues that drive mouse infection, J Virol

Li, Xu, Zhang, Su, Han et al., A spike-targeting bispecific T cell engager strategy provides dual layer protection against SarS-CoV-2 infection in vivo, Commun Biol

Liao, Wang, Tang, Yang, Duan et al., Human transferrin receptor can mediate SarS-CoV-2 infection, Proc Natl acad Sci USa

Liu Fl, Wu, Sun, Duan, Quan et al., rapid generation of aCE2 humanized inbred mouse model for CoVID-19 with tetraploid complementation, Natl Sci rev

Lu R, Zhao, Li, Niu, Yang et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding, lancet

Lu T, Zhang, Li, Wei, Sadewasser et al., Human angiotensin-converting enzyme 2-specific antisense oligonucleotides reduce infection with SarS-CoV-2 variants, J allergy Clin Immunol

Luo, Zhang, Kreutzberger Ajb, Eaton A, Edwards Rj, Jing et al., an antibody from single human V H -rearranging mouse neutralizes all SarS-CoV-2 variants through Ba.5 by inhibiting membrane fusion, Sci Immunol

Mazzarella L, Santoro, Fumagalli, Massa, Gavilán et al., Inhibition of the lysine demethylase lSD1 modulates the balance between inflammatory and antiviral responses against coronaviruses, Sci Signal

Meier, Becker, Levine, Dufresne, Foster et al., timing matters in the use of renin-angiotensin system modulators and CoVID-related cognitive and cerebrovascular dysfunction, PloS one

Mercado-Gómez, Prieto-Fernández, Goikoetxea-Usandizaga, Vila-Vecilla L, Bravo et al., the spike of SarS-CoV-2 promotes metabolic rewiring in hepatocytes, Commun Biol

Mfl, Blecha, Rr, Peng, Zuo, Cyclic 68 Ga-labeled peptides for specific detection of human angiotensin-converting enzyme 2, J Med Virol

Ml, Liu Fl, Sun, Li, He et al., SarS-CoV-2-triggered mast cell rapid degranulation induces alveolar epithelial inflammation and lung injury, Signal transduct target ther

Mt, Jiang, Chen, Badeti, Wang et al., S309-Car-NK cells bind the omicron variants in vitro and reduce SarS-CoV-2 viral loads in humanized aCE2-NSG mice, J Virol

Park, Lee, Kim, Jeon, Kim et al., a humanized aCE2 mouse model recapitulating age-and sex-dependent immunopathogenesis of CoVID-19, J Med Virol

Perumal R, Shunmugam L, Naidoo, Karim, Wilkins, Garzino-Demo A et al., Long COVID: A review and proposed visualization of the complexity of long CoVID, Front Immunol

Phoolcharoen, Shanmugaraj, Khorattanakulchai, Sunyakumthorn, Pichyangkul et al., Preclinical evaluation of immunogenicity, efficacy and safety of a recombinant plant-based SarS-CoV-2 rBD vaccine formulated with 3M-052-alum adjuvant, Vaccine

Prakash, Srivastava R, Coulon, Nr, Chentoufi, Tifrea et al., Genome-wide asymptomatic B-Cell, CD4 + and CD8 + t-cell epitopes, that are highly conserved between human and animal coronaviruses, identified from SARS-CoV-2 as immune targets for pre-emptive pan-coronavirus vaccines

Radzikowska, Ding, Tan, Zhakparov, Peng et al., Distribution of aCE2, CD147, CD26, and other SarS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, CoPD, obesity, hypertension, and CoVID-19 risk factors, allergy

Rai, Kumar, Deekshit, Karunasagar, Karunasagar, Detection technologies and recent developments in the diagnosis of CoVID-19 infection, appl Microbiol Biotechnol

Rodrigues Ts, Caetano, De Sá, Becerra, Dpa et al., CaSP4/11 contributes to NlrP3 activation and CoVID-19 exacerbation, J Infect Dis

Scholkmann, Ca, CoVID-19, post-acute CoVID-19 syndrome (PaCS, 'long CoVID') and post-CoVID-19 vaccination syndrome (PCVS, 'post-CoVIDvac-syndrome'): Similarities and differences, Pathol res Pract

Sefik, Israelow, Mirza, Zhao, Qu et al., a humanized mouse model of chronic CoVID-19, Nat Biotechnol

Sefik, Israelow, Zhao, Qu, Song et al., a humanized mouse model of chronic CoVID-19 to evaluate disease mechanisms and treatment options

Sefik, Qu, Junqueira, Kaffe, Mirza et al., Inflammasome activation in infected macrophages drives CoVID-19 pathology, Nature

Silva-Santos, Pagni Rl, Gamon, Bielavsky, Mlg et al., lisinopril increases lung aCE2 levels and SarS-CoV-2 viral load and decreases inflammation but not disease severity in experimental CoVID-19, Front Pharmacol

Snouwaert, La, Nguyen T, Dr, Schäfer et al., Human aCE2 expression, a major tropism determinant for SarS-CoV-2, is regulated by upstream and intragenic elements, PloS Pathog

Song, Washington, Hsu, Bae, Haelterman et al., Generation of a humanized mace2 and a conditional haCE2 mouse models permissive to SarS-CoV-2 infection, Mamm Genome

St, Ta, Pillai, Khanna, Lc, Galectin-9 protects humanized-aCE2 immunocompetent mice from SarS-CoV-2 infection, Front Immunol

Subramaniam, Kenney, Jayaraman A, O'connell Ak, Walachowski, Montanaro et al., aging is associated with an insufficient early inflammatory response of lung endothelial cells in SarS-CoV-2 infection, Front Immunol

Sun R, Zhao, Fu, Wang, Guo et al., Humanized mice for investigating SarS-CoV-2 lung infection and associated human immune responses, Eur J Immunol

Sun, Chiu, Wu, Lee, Hu et al., Development of aaV-delivered broadly neutralizing anti-human aCE2 antibodies against SarS-CoV-2 variants, Mol ther

Sursal, Gandhi, Feldstein, Frid, Kefina et al., Significant mortality associated with CoVID-19 and comorbid cerebrovascular disease: a quantitative systematic review, Cardiol rev

Tai, Feng, Chai, Lu, Zhao et al., an mrNa-based t-cell-inducing antigen strengthens CoVID-19 vaccine against SarS-CoV-2 variants, Nat Commun

Tu, Fang, Yang, Zhang, Sun et al., a murine model of DC-SIGN humanization exhibits increased susceptibility against SarS-CoV-2, Microbes Infect

Upadhyay, Suryawanshi Rk, Mccavitt-Malvido, Kumar Rg, Murray et al., J and Grover M: Colonic expression of ace2, the SarS-CoV-2 entry receptor, is suppressed by commensal human microbiota, Gut Microbes

Vanhove, Marot, Rt, Gaborit, Evanno et al., XaV-19, a swine glyco-humanized polyclonal antibody against SarS-CoV-2 spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants, Front Immunol

Verma, Ana-Sosa-Batiz, Shafee, Maule, Pba et al., Influence of Th1 versus Th2 immune bias on viral, pathological, and immunological dynamics in SarS-CoV-2 variant-infected human aCE2 knock-in mice, EBioMedicine

Wang, Dou, Shi R, Duan, Liu, Zhang et al., Etesevimab in combination with JS026 neutralizing SarS-CoV-2 and its variants, Emerg Microbes Infect

Weingarten-Gabbay, Klaeger, Sarkizova, Pearlman Lr, Chen et al., Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame orFs, Cell

Weiss, Liu, Ball, Hoover Ar, Wong Ts et al., N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SarS-CoV-2, PloS one

Wu, Qin, Huo, Liang, Yang et al., CD147 contributes to SarS-CoV-2-induced pulmonary fibrosis, Signal Transduct Target Ther

Xiong, Zhang, Class, Ab, Interleukin-1RA mitigates SARS-CoV-2-induced inflammatory lung vascular leakage and mortality in humanized K18-haCE-2 mice, arterioscler thromb Vasc Biol

Yang, Wang, Zhu, Wu, Li et al., a non-aCE2 competing human single-domain antibody confers broad neutralization against SarS-CoV-2 and circulating variants, Signal transduct target ther

Ye, Zhou, He, Yang, Zhang et al., SarS-CoV-2 infection in the mouse olfactory system, Cell Discov

Yinda, Jr, Bushmaker, Purushotham, Va et al., K18-haCE2 mice develop respiratory disease resembling severe CoVID-19, PloS Pathog

Yong, De, Sy, Tan, Lf, Comparison of infection and human immune responses of two SarS-CoV-2 strains in a humanized haCE2 NIKo mouse model, Sci rep

Yu, Li, Xiao, Hu, the histamine receptor H1 acts as an alternative receptor for SarS-CoV-2, mBio

Zayou L, Prakash, Vahed, Nr, Quadiri A, Belmouden A, Lemkhente et al., Dynamics of spike-specific neutralizing antibodies across five-year emerging SARS-CoV-2 variants of concern reveal conserved epitopes that protect against severe CoVID-19, Front Immunol

Zhang L, Dutta, Xiong, Chan, Chan, Tm et al., Engineered aCE2 decoy mitigates lung injury and death induced by SarS-CoV-2 variants, Nat Chem Biol

Zhang L, Dutta, Xiong, Chan, Chan, Tm et al., Engineered high-affinity aCE2 peptide mitigates arDS and death induced by multiple SarS-CoV-2 variants

Zhang T, Magazine, Mcgee, Carossino, Veggiani, Kousoulas et al., th2 and th17-associated immunopathology following SarS-CoV-2 breakthrough infection in Spike-vaccinated aCE2-humanized mice, J Med Virol

Zhang, Fang, Zhang, Han, Wang et al., Humanized major histocompatibility complex transgenic mouse model can play a potent role in SarS-CoV-2 human leukocyte antigen-restricted t cell epitope screening, Vaccines

Zhang, Ma, Sun, Zhou, Xie et al., Exploring gut-lung axis crosstalk in SarS-CoV-2 infection: Insights from a haCE2 mouse model, J Med Virol

Zhao, Wl, Yang, Zhang, Huang et al., Cathepsin l plays a key role in SarS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development, Signal transduct target ther

Zhu, Sharma, Boghani, Sarcan, George et al., Pujhari S and rasgon Jl: Mice with humanized-lungs and immune system-an idealized model for CoVID-19 and other respiratory illness, Virulence

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"key20260112082423_b56-MI-6-1-00293" }, { "DOI": "10.1002/adhm.202302803", "article-title": "Conversion of host cell receptor into virus destructor by immunodisc to neutralize diverse SARS-CoV-2 variants", "author": "Hwang", "doi-asserted-by": "publisher", "issue": "e2302803", "journal-title": "Adv Healthc Mater", "key": "key20260112082423_b57-MI-6-1-00293", "volume": "13", "year": "2024" }, { "author": "Dong", "key": "key20260112082423_b58-MI-6-1-00293" }, { "DOI": "10.1128/mbio.01088-24", "article-title": "The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2", "author": "Yu", "doi-asserted-by": "publisher", "issue": "e0108824", "journal-title": "mBio", "key": "key20260112082423_b59-MI-6-1-00293", "volume": "15", "year": "2024" }, { "DOI": "10.1016/j.apsb.2024.05.026", "article-title": "Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics", "author": "Chan", "doi-asserted-by": "publisher", "first-page": "4028", "journal-title": "Acta 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