Table 4.
Animal models of Lassa fever
| Species | Animal model | Strains | Dose | Route | Lethality | Signs of Disease | Strengths/Weaknesses | References |
|---|---|---|---|---|---|---|---|---|
| Rodents | Neonatal mice | – | 100 TCID50 | IP | No | No | Natural host/No clinical signs or lesions | 238 |
| CBA mouse | Josiah | 103 PFU | IC | 70–100% | Weight loss, immobility, scruffy fur, seizures, severe decubitus paralysis | Applied in drug evaluation/Immunodeficient and inapplicable to immune correlates | 239 | |
| HHD mouse | Ba366 | 106 PFU | IV | 22% | Ruffled fur, lethargy, high level viremia, elevated AST level, severe pneumonitis | Model for pathogenesis study/Immunodeficient and inapplicable to immune correlates | 246 | |
| STAT1−/− mouse | Josiah | 103 PFU | IP | 100% | Fever, weight loss, SNHL, viremia | Model for pathogenesis study/Barrier environment needed, MHC-related, age-associated, injection route-dependent pathogenicity, distinguishing characteristics of the human immune system, not applicable to live vaccine evaluation | 241,242,245 | |
| LF2384 | 105 PFU | 80% | ||||||
| LF2450 | 105 PFU | 50% | ||||||
| IFNAR−/− mouse |
Josiah/AV Ba366/Nig04-10 |
103 PFU | IV | No | Weight loss, persistent viremia, ruffled fur, hypoactivity | 240–243 | ||
| Chimeric IFNAR−/− B6 mouse |
Ba366/Ba298 NNig04-10/Nig-CSF |
103 PFU | IP | 100% | Weight loss, vascular leakage | 242,244 | ||
| Inbreed Strain13 guinea pig | Josiah | 104 TCID50 | SC IP | >90% | Fever, weight loss, ruffled fur, hunched posture, pneumonia, pneumorrhagia | Obvious clinical symptoms, natural susceptibility/Distinguishing characteristics of the human immune system | 238,251,–253,256,258 | |
| Z-132 | IP | 100% | ||||||
| Soromba-R | IP | 0~57% | ||||||
| Pinneo | IP | No | Mild to moderate disease | |||||
| NJ2015 | 104 PFU | SC | No | Fever, weight loss, conjunctivitis | ||||
| Outbreed Hartly guinea pig | Josiah | SC IP | 30~67% | Fever, weight loss, hypothermia neutropenia, lymphopenia, thrombocytopenia | Accessibility, obvious clinical symptom/viral adaptation required and addition mutants acquired | |||
| GPA-Josiah | 103 TCID50 | IP | 100% | |||||
| LF2384 | 104 PFU | IP | 100% | |||||
| Nonhuman primates | Squirrel monkey | Bah | 106.8 TCID50 | IM | 25% | Anorexia, lassitude, depression, polydipsia | Small size and available NHP/Individuals heterogeneity | 273 |
| Marmoset | Josiah | 106 PFU | SC | 100% | Fever, weight loss, viremia, depression, anorexia | Small size, lower caging and feeding costs/variable clinical course | 271 | |
| Rhesus monkey | Josiah | 106.1 PFU | SC | 50–60% | Cough, fever, weight loss, rash, hiccups, lethargy, aphagia, huddled posture, constipation, conjunctivitis, anorexia, decreased water intake, bleeding from the gums and nares | Accurately simulate clinical signs of human/ethical concerns, high cost, inaccessible | 262,263,314 | |
| Cynomolgus macaque | Josiah | 104 PFU | IM | 100% | Fever, weight loss, lethargy, anorexia, rashes, facial edema, hunched posture, ruffled fur, piloerection, bleeding from puncture sites, dehydration, epistaxis, acute respiratory syndrome, neurological signs, deafness | Simulate sever cases of human infection/Ethical concerns | 253,264–270,289–292 | |
| Z-132 | 104 PFU | IM | 100% | |||||
| Soromba-R | 104 TCID50 | IM | 66% | |||||
| Surrogate models | Inbreed Strain13 guinea pig | Pichinde virus | >3 PFU | SC | 100% | Weight loss, ruffled fur, rapid breathing, hypoactivity, decreased appetite | Obvious clinical symptoms, natural susceptibility/difficult to obtain, potential difference between original strains | 277,278 |
| Outbreed Hartly guinea pig | Pichinde virus/P18 | 100 PFU | IP | 100% | 274 | |||
| Outbred hamsters | Pirital virus | 105 TCID50 | IP | >50% | Moribund, hemorrhage, pneumonia | Models for studying the mechanism of hepatic injury/Potential differences between Pichinde virus and LASV | 248 | |
| LVG/Lak hamsters | Pichinde virus | 500 PFU | SC | 0–100% | Not mentioned | Accessibility/Neonatal or Immunosuppression needed to render lethal infections in adult animals, less susceptible to Pichinde virus compared with MHA/Lak hamsters | 247 | |
| MHA/Lak inbred hamsters, | 35/3.5 × 104/3.5 × 106 PFU | IP | 100% | Susceptible to lethal virus infection in both newborns and adult animals/Potential differences between Pichinde virus and LASV |
TCID50 median tissue culture infective dose, PFU plaque formation unit, IP intraperitoneal, IC intracranial, IV intravenous, SC subcutaneous, IM intramuscular, SNHL sensorineural hearing loss, NHP nonhuman primate, – not applicable