Table 1.
Summary of DENV infection in animal models
| Animal model | Immune status | DENV serotypes | Inoculation routes | Inoculation dose | Strengths | Limitations | References |
|---|---|---|---|---|---|---|---|
| C57BL/6 and BALB/c mice | Immunocompetent | DENV-2, DENV-3 | IP, IV |
Variable (1 × 104 – 1 × 105 PFU; 104 TCID50 |
Useful in the study of immunopathogenesis | Very low viremia; no clinical manifestations | [27, 87, 129, 130] |
| AG129 mice | Immunodeficient | DENV-1 to DENV-4 | SC, IP |
Variable (1 × 103 – 1 × 107 PFU) |
Allows for infection by all four DENV serotypes; allows antibody-mediated protection; production of ADE phenomenon; immunogenicity and protection testing | No overt clinical manifestations; limited immune response may not reflect natural infections; age-dependent disease severity | [7, 14, 74, 84, 102, 103, 127, 134] |
| Humanized mice | Immunodeficient | DENV-2 | SC, ID, IP, IV, mosquito |
Variable (1 × 104.7 – 1 × 108 PFU) |
Clinical manifestations develop (viremia; thrombocytopenia occurs); suitable for the study of the pathogenesis of dengue fever; potentially useful for drug and vaccine development | Mouse-to-mouse variations; limited immune response | [3, 9, 26, 28, 52, 79, 80] |
| Rhesus monkey | Immunocompetent | DENV-1 to -4 | SC |
Variable (1 × 103.7 – 1 × 107 PFU) |
Sustains viral replication; course of infection resembles DENV infection in humans; production of immune response and vaccine efficacy testing; ADE effect | High costs; low viremia; does not develop vascular leaks, DHF, or DSS | [12, 30, 35, 43, 69, 72] |
| Marmoset | Immunocompetent | DENV-1 to -4 | SC |
Variable (1.8 × 103 – 6.7 × 107 PFU) |
High plasma viral load; cellular and humoral immune response | No overt clinical signs | [76, 85, 131] |
| Bonnet macaque | Immunocompetent | DENV-4 | IV | 1 × 106 PFU |
High viremia (2.2–4.0 × 106 copies/mL); antibody response |
No clinical symptoms | [56] |
| Chimpanzee | Immunocompetent | DENV-1 to -4 | SC, ID | 103-106 PFU | Detectable viremia; immune response (nAb production) | No overt clinical signs | [73, 106] |
|
Swine (Yucatan miniature pig) |
Immunocompetent | DENV-1 | SC, IV | 1 × 105 or 1 × 107 PFU | Viremia; Ab production; skin rash (IV inoculation) | No overt clinical signs | [21, 98] |
| Tree shrew | Immunocompetent | DENV-2, DENV-3 | IV, SC | 1.5 × 103 PFU | Induces rise of body temperature, modest thrombocytopenia; may be suitable for the evaluation of antivirals and vaccines | Very low viremia; no manifestations of severe dengue | [53] |
PFU, plaque-forming units; TCID50, median tissue culture infectious dose; IV, intravenous; SC, subcutaneous; ID, intradermal; IP, intraperitoneal