Table 8.
Animal models of CCHFV
| Species | Animal model | Pathogens | Max. Dose | Route | Lethality | Signs of disease | Strengths/weaknesses | References |
|---|---|---|---|---|---|---|---|---|
| Mice | Neonatal mice | IbAr 10200 | 50 LD50 | IP | 100% | Viraemia and death | Obvious symptoms/Lacking of full immune function | 911 |
| IFNAR−/− C57BL/6 mice | IbAr 10200 | 104 TCID50 | IP/IN/IM/SC | 100% | Weight loss, ruffled hair, hunchback and lethargy | Highly susceptible to CCHFV and clinical signs similar to human patients/Lacking of important innate immune pathways | 569,570,912 | |
| STAT-1 knockout mice | IbAr 10200 | 103 PFU | IP | 100% | Lethargy, piloerection, and hunched posture, fever | 913 | ||
| IFNα/β/γR−/− mice | Ank-2 strain | 100 TCID50 | IP | 100% | Weight loss, ruffled fur, depression and nasal/ocular discharge | 914 | ||
| SGM3 humanized mice | Oman-199809166 | 104 TCID50 | IP | 0 | Minimal weight loss and recovered | Disease process similar to humans/Time consuming and expensive | 572 | |
| Turkey-200406546 | 104 TCID50 | IP | 100% | Weight loss and severe neurological disease | ||||
| Mice adapted, Male mice | Hoti | 104 TCID50 | IP | 0–100% (age-dependent) | Weight loss, piloerection, hunched posture, and lethargy | Immunocompetent animal model, gender and age-associated disease severity/Additional mutants introduced by virus adaptation | 573 | |
| Hamsters | STAT-2 knockout hamsters | IbAr10200 | 104 TCID50 | IP/IM/SC | 100% | Petechial rash, blood coagulation dysfunction, and biochemistry and blood cell count abnormalities | Applicable for pathogenesis study and recapitulated hallmarks of human disease/Immunodeficient and inapplicable for evaluating immune correlates | 915 |
| Nonhuman primates | Cynomolgus macaques | Afghan09-2990 | 106.2 PFU | IV | 0 | Largely uniform and mild disease state | Immunocompetent animal model, similar to human transmission, organ pathology, and disease progression/not consistently lethal, inaccessibility and ethical issues | 576,916 |
| Kosova Hoti | 105 TCID50 | IV/SC/SC + IV | 0–75% | Thrombocytopenia, hypoproteinemia, edema and epistaxis |
IP intraperitoneal, SC subcutaneous, IV intravenous, IM intramuscular, IN intranasal, PFU plaque-forming units, TCID50 median tissue culture infective dose, CCHF Crimean-Congo hemorrhagic fever, CCHFV Crimean-Congo hemorrhagic fever virus, – not applicable