Humanized Mice in Dengue Research: A Comparison with Other Mouse Models
Abstract
:1. Introduction
1.1. Virus
1.2. Epidemiology
1.3. Immune Response and Pathogenesis of Dengue Virus
2. Mouse Models for Dengue Research
2.1. Wild Type Mouse Models
2.2. Knockout Mouse Models for the Study of DENV
2.2.1. AG129
2.2.2. STAT
2.2.3. C57BL/6 DKO, TKO, Irf1−/−, Ifnar1−/−, TNF−/−, and CCR5−/−
2.3. Transgenic Non-Humanized Model of DENV
C57BL/6J hTNF+++, IFNα/βR−/− Tg, Tg HLA-A*02:01, and B10.Tg HLA-DR3
2.4. Humanized Mouse Models of DENV
2.4.1. SCID
2.4.2. NOD/SCID, and NSG
2.4.3. NSG-BLT and NOD/SCID-BLT
2.4.4. NSG HLA Class I Transgenic Strains, Expressing A2 Haplotypes
2.4.5. NSG-SGM3 and NOG-EXL Mouse Model
2.4.6. NRG
2.4.7. RAG2 and DRAG
3. Mouse Models for the Development of Dengue Vaccines
3.1. Mouse Models to Test Safety and Immunogenicity of DENV-Vaccine Candidates
3.2. Humanized Mice Models for the Development of Dengue Vaccines
3.2.1. Hu-NSG
3.2.2. BLT-NSG
3.2.3. Hu-DRAG
3.2.4. Ideal Humanized Mouse Model for DENV Pathogenesis Studies and Vaccine Development
4. Treatment
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Mouse Model | Route | Asymptomatic Infection | Neurologic Signs | Hematological Changes | Disease Signs | Pro-Inflammatory Cytokines | Ref. |
---|---|---|---|---|---|---|---|
BALB/c | IP, I.C. | NR | Yes | Yes | NR | [74] | |
A/J | IV | NR | Yes | Transient thrombocytopenia | NR | NR | [71] |
IV | Yes | Yes | Transient ↑ hematocrit and ↓ WBC count | NR | NR | [90] | |
IV | NR | Yes | Hematocrit: Slight ↑ | NR | NR | [91] | |
IV | NR | NR | NR | Vascular permeability: High | NR | [92] | |
IV | NR | Yes | NR | Yes | IFN-γ: ↑ | [93] | |
IP | NR | NR | NR | Yes | IFN-γ, IL-6, IL-12, TNF-α: ↑ | [94] | |
IP | Yes | Yes | ↑ levels of transaminases | Vascular leakage: High | IFN-γ, IL-6 and TNF-α: ↑ | [77,95] | |
IP | Yes | Yes | Early leukopenia | Yes | IL-1α, IL-6, IL-12p40, IL-17A, IFN-γ and TNF-α: ↑ | [96] | |
IP | NR | NR | Thrombocytopenia | Plasma leakage | IL-2, IL-4, and TNFα: ↑ | [97] | |
IP | NR | NR | Coagulopathy | Plasma leakage | IL-2, IL-4, and TNFα: ↑ | ||
IP | NR | NR | Thrombocytopenia | Plasma leakage | IL-1α, IL-6, IL-10, IL-12p40, IFN-γ and G-CSF: ↑ | [80] | |
IP | NR | Yes | Leukopenia Thrombocytopenia | Yes | IL-1α, IL-6, IL-10, IL-12p40, IFN-γ, and G-CSF: ↑ | [98] | |
A129 | IV | NR | Yes | NR | Yes | IFN-γ: ↑ | [93] |
IV | NR | Yes | NR | Yes | TNF-α and IL-10: ↑ | [99] | |
IV | NR | NR | Thrombocytopenia and Lymphopenia: Moderate AST: Elevated | Severe liver damage Vascular leakage Middle | DENV-2: IL-6: ↑ | [100] | |
IFNAR−/− | IV | NR | Yes | NR | NR | TNF-α and IL-10: ↑ | [99] |
IV | NR | NR | NR | Yes | NR | [52] | |
IP | NR | NR | NR | Yes | IL-6, INF-α, IP10, IFN-a, IFN-γ: ↑ | [101] | |
Cardif−/− C57BL/6 | IV | Yes | NR | NR | NR | IFN-α: ↑ | [102] |
STAT1−/− | IV | NR | NR | NR | NR | IFNα: ↓ IFNβ: ↑ | [81] |
IC | NR | Yes | NR | Yes | NR | [103] | |
STAT2−/− | IV | NR | NR | NR | IFNα: ↓ IFNβ: ↑ | [81] | |
STAT1−/− STAT2−/−and STAT1−/− IFNAR−/− | IV | NR | NR | NR | NR | IFNα: ↓ IFNβ: ↑ |
Mouse Model | Route | Hematological Changes | Disease | Immune Response | Ref | ||
---|---|---|---|---|---|---|---|
Pro-Inflammatory Cytokines | Cellular Response | Humoral Response | |||||
NSG mice also known as:
| ID | Thrombocytopenia: High | Yes | IFN-γ, TNF-α, IL-2 and VEGF: ↑ | CD4 Th1, TH2 and B cells | NR | [65] |
ID, Mosquito | Thrombocytopenia | NR | IFN-γ, IL-4, Il-10: ↑ | NR | IgM, IgG, IgA | [121] | |
SC | Thrombocytopenia | Yes | NR | NR | IgM, IgG, IgA | [109] | |
IV | Thrombocytopenia: High hTPO; Middle Megakaryocytes: ↓ | NR | NR | NR | NR | [110] | |
SC, IP | NR | NR | NR | CD4+ | IgM | [115] | |
NSG-BLT mice (HLA-A2) mice | SC | NR | Yes | IFN-γ: ↑ | CD8+ | IgM | [112] |
NSG-BLT | IV | Thrombocytopenia: (7 or 14 dpi) | Yes | IL-R1A, VEGF, IP10: ↑ (3dpi) | CD4+, CD8+ | IgM | [113] |
SCID-HuH-7 | IP | NR | NR | NR | NR | Neutralizing Antibodies | [106] |
RAG2−/− gamma c−/− | SC | NR | Yes | NR | NR | IgM, IgG | [119] |
NSG-Tg (HLA-A2/H2-D/beta2M)1DVs/Sz mice also known as: -NOD-scid IL2rgamma null TG (HLA-A2/HuBeta2M) | SC | NR | Yes | IFNγ, TNFα, IL-2: ↑ | NR | IgM, IgG, IgA | [115] |
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Coronel-Ruiz, C.; Gutiérrez-Barbosa, H.; Medina-Moreno, S.; Velandia-Romero, M.L.; Chua, J.V.; Castellanos, J.E.; Zapata, J.C. Humanized Mice in Dengue Research: A Comparison with Other Mouse Models. Vaccines 2020, 8, 39. https://doi.org/10.3390/vaccines8010039
Coronel-Ruiz C, Gutiérrez-Barbosa H, Medina-Moreno S, Velandia-Romero ML, Chua JV, Castellanos JE, Zapata JC. Humanized Mice in Dengue Research: A Comparison with Other Mouse Models. Vaccines. 2020; 8(1):39. https://doi.org/10.3390/vaccines8010039
Chicago/Turabian StyleCoronel-Ruiz, Carolina, Hernando Gutiérrez-Barbosa, Sandra Medina-Moreno, Myriam L. Velandia-Romero, Joel V. Chua, Jaime E. Castellanos, and Juan C. Zapata. 2020. "Humanized Mice in Dengue Research: A Comparison with Other Mouse Models" Vaccines 8, no. 1: 39. https://doi.org/10.3390/vaccines8010039