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. 2024 Sep 11;9:223. doi: 10.1038/s41392-024-01917-x

Table 2.

Animal models of filoviruses

Species Approaches/animals Pathogens Dose Route Lethality Signs of Disease Strengths/Weaknesses References
Mouse Neonatal mice EBOV 1 PFU IP 100% No No need for additional sensitive approaches/Not applicable for evaluation of immune correlates 59
Mice adapted virus EBOV Mayinga 102 PFU IP or IC 100% Ruffled fur, malaise, weight loss, and hemorrhage Target cells and tissue tropism comparable to humans/Only sensitive to IP injection, additional mutants introduced by adaptation 799
SC 0–100%
IFN-α/βR−/− mice maEBOV 103 PFU IP or SC 100% Lethargy, weight loss, anorexic and piloerection Lethality to wild type viruses, valuable for the pathogenesis study/Mimicking limited clinical features of infection, barrier conditions needed, not applicable to vaccine evaluation 58,70
EBOV Mayinga 103 PFU IP
EBOV E718 10 TCID50 IP or Aerosol
SUDV Boneface 103 PFU IP
MARV Popp 10 TCID50 IP or Aerosol
STAT1−/−mice maEBOV 103 PFU IP or SC 100% Ruffled fur, malaise, weight loss Lethality to wild type viruses, valuable for the pathogenesis study/Inconsistent clinical performance for different subtype of virus infections, barrier conditions needed, not applicable for vaccine evaluation 58,69,71
EBOV Mayinga 103 PFU IP 0
EBOV Kikwit 102 PFU IP 40%
SUDV Gulu 100%
BDBV 20%
MARV Angola 80%
SCID mice maEBOV/EBOV/SUDV 103 PFU IP or SC 100% Weight loss Natural susceptibility to specific isolates/Inconsistent susceptibility to different subtypes or isolates 58
gpaMARV Ravn
MARV Musoke 103 PFU IP 100% Ruffled fur, weight loss, anorexia, hunched posture Shorter time to death than other SCID mice model/Lack typical biochemical parameters 72,73
MARV Ravn
MARV Ci67
maMARV Angola 2.72 TCID50 IP 100% Weight loss
SCID mice maMARV-Ravn 103 PFU IP 100% Weight loss, ruffled fur, hunched posture, lethargy Exhibited most clinical hallmarks in humans/Time consuming, additional mutants introduced by virus adaptation 57,73
maMARV Angola 102 TCID50
Humanized mice EBOV Mayinga 105 TCID50 IP 100% Ruffled fur, weight loss, fever, and hunched posture, hypothermia, and moribundity Recapitulating disease severity of different EBOV subtypes in humans/Lack of disease hallmarks 76
EBOV Makona 103 FFU IN 92.86% 77
SUDV Gulu 71.43%
BDBV Bundibugyo 28.58%
TAFV Pauleoula 20%
RESTV 19.2%
EBOV Makona IM 56% 79
MARV-Angola 25% Weight loss, anemia Reveal how MARV modulate specific components of the immune system/Poor disease severity
Syrian hamster Hamster maEBOV 103 FFU IP 100% Ruffled fur, malaise, severe coagulation disorders Displaying most clinical hallmarks of EVD/Virus adaptation needed 82
STAT2−/−hamster MARV RAVV 105 PFU IP 0 Ruffled fur, lethargy, hunched posture, and weight loss Susceptibility to wild-type viruses/barrier conditions needed, not applicable for vaccine evaluation 84
MARV Musoke 100%
MARV Voege 100%
MARV Angola 80%
Hamster haMARV 103 PFU IP 100% Weight loss, fever, rash, coagulation abnormalities, and hemorrhagic Recapitulating most clinical hallmarks in humans/Virus adaptation needed 85
Guinea pig Guinea pig gpaEBOV Mayinga 104 PFU SC/IP 100% Fever, weight loss, diarrhea, anorexia, ataxia, hemorrhage, ceased eating, dehydration Similar disease features to humans/Additional mutants induced by virus adaptation 87,89
gpaSUDV 103 TCID50 IP 100% Weight loss, coagulation disorders 91
gpaMARV Angola/Ravn 5000 PFU IP 100% Weight loss, fever, and hypothermia Differentiated pathogenicity among MARV strains/Additional mutants induced by virus adaptation 93
Ferret – EBOV Kikwit 103 PFU IN 100% Hypothermia, rash, hemorrhage, weight loss, depression, diarrhea, dehydration, nasal and ocular discharge, dyspnea, hunched posture, and altered gait Uniform lethality with wild type viruses, low dose needed, susceptible to multiple challenge routes/Inconsistent clinical performance for different subtype of virus infections compared with humans, lack of apparent disease following ocular challenge, lack of disease hallmarks 96
SUDV Gulu
BDBV
rgEBOV-C07 1 PFU IM 97
EBOV Makona-C07 200 TCID50 IM or IN 100% Rash, fever, weight loss, and coagulation disorders 98
BDBV 159 TCID50 IM
EBOV 13.3 PFU Oronasal 100% Rash, fever, weight loss, lethargy, unkempt appearance, dyspnea, diarrhea, and coagulation disorders 99
76.6 PFU Oral
76.6 PFU Ocular 0 No
SUDV Boneface 1260 TCID50 IM or IN 100% Fever, weight loss, malaise, anorexia, dyspnea, absence of urine, diarrhea, and coagulation disorders 100
RESTV IM 103
IN
gpaEBOV 104 PFU IP 100% Weight loss, anorexia, fever, hemorrhages and rash 892
NHPs Rhesus monkey EBOV 103 FFU IM 67–100% Fever, multiple organomegaly, pancytopenia, and coagulation disorders Naturally, susceptible model/Mimicked limited physiological features of infection, expensive and ethical issues 83,107–109,112
SUDV Gulu 103 FFU IM 91% Fever, depression, rash, anorexia, dyspnea, dehydration, shock and multiorgan failure Recapitulate the disease course seen in human, aerosolized exposure model/Expensive and ethical issues 116
SUDV Boniface 500 PFU Aerosol 100% 117
BDBV 200706291 103 PFU IM 40% Fever, anorexia, macular rash, depression Models for immune signatures/Expensive and ethical issues 119
MARV Angola/Musoke 103 FFU IM 100% Hemorrhagic Varied susceptibility to differently virulent strains/Expensive and ethical issues 120,893,894
Rhesus monkey MARV-Ozolin/Ravn/Angola 103 FFU/PFU IM/Aerosol 0–100% Fever, lymphadenopathy, anorexia, malaise, edema, dehydration and rash Varied susceptibility to differently strains, aerosolized MARV exposure model/Expensive and ethical issues 120,121,893,894
Cynomolgus macaque EBOV Kikwit EBOV Mayinga 104 PFU Conjunctival 40%~100% Weight loss, fever, anorexia, and hypothermia Mucosal (Conjunctival) exposure model/Expensive and ethical issues 128,133
Oral 40%~60% Ruffled fur, Weight loss, fever, anorexia, malaise hypothermia, petechia, dehydration, rash Mucosal exposure model, obvious gastrointestinal symptoms in IN exposed group, recapitulating the hallmark features of human disease/Do not reflect the difference in virulence between strains, expensive and ethical issues 128,133,134
64 PFU IN 100%
74 PFU IM
104 PFU IM
EBOV Makona 104/100 PFU IM/Oral/IN 100% Malaise, fever, weight loss, rash, lymphadenopathy, anorexia, motor dysfunction, coagulopathy, and hypothermia Recapitulating the hallmark features of human disease, Mucosal exposure model/Do not reflect the difference in virulence between strains, expensive and ethical issues 129,132,134
SUDV Gulu 103 PFU IM 100% Fever, weight loss, malaise, diarrhea, dehydration, bleeding, petechia, anorexia, reduced stool output, rash Rapid systemic disease/Significant difference in clinical signs among infected macaques 136,895
RESTV 5 × 103 PFU SC 83% Anorexia, fever, weight loss, nasal discharge, hemorrhages. Predict interspecies transmission potential of RESTV/Not recapitulating the hallmark features of human RESTV disease 145
MARV Angola 103 FFU IM 100% Severe MHF Varied susceptibility to differently virulent strains/Expensive and ethical issues 120,131,150
MARV Musoke 50% Severe MHF
MARV Ozolin 0 Fever, hunched posture, and anorexia
African green monkey EBOV 103 PFU Aerosol 100% Fever, anorexia, dehydration, lymphadenopathy Aerosolized model/Lack of rash and behavioral changes
SUDV Boniface 500 PFU Aerosol 100% Fever, anorexia, malaise, depression, rash, dyspnea, reduced urine and fecal output, dehydration Aerosolized model/No pronounced changes in hematology 117
EBOV Kikwit 106 TCID50 Aerosol 92% Fever, ruffled fur, malaise, dyspnea, anorexia, hemorrhage Aerosolized model/Rapid onset of symptoms and death 152,153
Marmoset monkey EBOV Kikwit 103 PFU IM 100% Fever, weight loss, anorexia, depression, and reduced stool output Small NHP model/Lack of widespread intravascular coagulation 152,153
MARV Musoke 152
Baboon gpaEBOV 100 PFU SC 100% Weight loss, hyperthermia, anorexia, adynamia, ataxia, abasia, rash, diarrhea, dyspnea, and hemorrhages Recapitulating the hallmark features of human disease/virus adaptation needed 155
Surrogate model Neonatal Mice rVSVΔG-ZEBOV-GP 103 TCID50 SC 100% Tremors, widened stance, ataxia, seizures and paresis and/or paralysis Model for neurologic and ocular symptoms, models in BSL-2 conditions/Data cannot be directly extrapolated to humans 156,158
Hamsters rVSVΔG-ZEBOV-GP 103–106 PFU IP 33–100% Weight loss Models in BSL-2 conditions, model for entry of EBOV or MARV depends on glycoproteins/Detailed pathogenesis of the disease different from EBOV and MARV infection 159
rVSVΔG-MARV-GP 105.5–107.5 PFU 25–100%

EBOV ebola virus, PFU plaque forming unit, IP intraperitoneal, IC intracutaneous, SC subcutaneous, IFN interferon, SUDV Sudan virus, MARV Marburg virus, STAT signal transducer and activator of transcription, BDBV Bundibugyo virus, TAFV Taï Forest virus, RESTV Reston virus, FFU focus-forming unit, IN intranasal, IM intramuscular, TCID50 50% tissue culture infective dose, ma mouse-adapted, scida SCID mouse-adapted, ha hamster-adapted, gpa guinea pig-adapted, rg reverse-genetics, BSL-2 biosafety level 2, – not applicable