Review Article

Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

Table 2

Animal models for the evaluation of arenavirus pathogenesis and countermeasure protective efficacy.

VirusAnimal model/strainVirus strainVirus doseRoute(s) of infection%
lethality
Time to death
(days)
Salient featuresReference

OW LASVGuinea pig/Strain 13Jos, Z-132, and Sor≥2 PFU,
1 × 104 TCID50 some studies
s.c., i.p., and i.m.60% (Sor)–100% (Jos, Z-132)11–22 (Jos, Z-132), >17 days (Sor)interstitial pneumonia, Sor strain less virulent[101, 102, 109]
Guinea pig/HartleyJos≥2 PFUs.c., i.p.<30% (s.c.)
~67% (i.p.)
15–24Viremia, seroconversion[109, 110]
Macaque Jos, Z-132, and Sor1 × 104 TCID50i.m., aerosol 57% (Sor)–100% (Jos, Sor)12–19Viremia, interstitial pneumonia, vasculitis, and occasional virus shedding[101, 110117]
MarmosetJos1 × 103–1 × 106 PFUs.c.Unknown (animals euthanized)Unknown
(severe morbidity 15–20 days)
Hepatic necrosis, lymphoid depletion, and interstitial nephritis[118, 119]
Mastomys natalensis UnclearUncleari.p.NoneNonePersistent infection[110]


LUJV
Guinea pig/Strain 13NA10–100,000 FFUi.p.100%11–16Weight loss, virus in multiple organs, leukopenia, thrombocytopenia, elevated transaminase levels, and animal age 52–78 weeks[108]
MacaquesNA10,000 TCID50i.m.Not lethalNot lethalMild illness, delayed inflammatory response[120]

NWJUNVGuinea pig/Strain 13Rom, XJ1,000–6,000 PFUi.p.0–100%
(strain specific)
100% (Rom), 0% (XJ)Weight loss, elevates AST/PLT levels, thrombocytopenia[83]
Guinea pig/HartleyMultiple, Rom (most lethal)1–5,000 PFUi.p., i.n., i.m., and oral0–100%
(strain specific)
Hemorrhagic strains; 12–19, neurological strains; >20, attenuated strains; no deathStrain dependent: neurological and/or hemorrhagic, leukopenia, thrombocytopenia, and interferon-alpha production[7983, 85, 8993]
Neonatal miceXJ13, can#1, reassert, and gene replacements500 TCID50i.c.0–100%<28Death is inconsistent with human disease, strain Can#1 is not lethal[121]
Mice/type I IFN α/β and gamma receptor KORom10,000 PFUi.p.Unclear; all euthanized with severe disease~13.5
(unclear; all euthanized with severe disease)
Viremia, viral dissemination[122]
MacaqueRom, Esp, and Led10,000–100,000 PFUi.m.0% (Rom)
100% (Esp)
Day 33 (Esp)Espindola; hemorrhagic, Ledesma; neurological manifestations[106, 107, 123126]
MarmosetXJ1,000 TCID50i.m.100%22–32Anorexia, decrease in weight, leukopenia, thrombocytopenia, viremia, hemorrhage of the gums, pharynx, esophagus abdominal cavity, and neurological illness[127130]
Calomys musculinus An9446100 TCID50i.n. ~70% (newborn)
~100% fetus
Day 24–40 (newborn)Persistent infection model, impacts adult fertility[131134]
MACVGuinea pig/Hartley Car, Chi10,000 PFUi.p.0–80%18–23 daysWeight loss, decreased activity, and strain 13 animals also attempted[9497]
Mice/type I IFN α/β and gamma receptor KOCar, recombinant Car10,000 PFUi.p.100%23-24Viremia, neuronal damage, and recombinant virus as lethal as wild-type[135]
Mice/STAT KOCar1,000 PFUi.p.100%7.3 Elevated cytokines [136]
MacaqueCar, Chi1,000–100,000 PFUi.m., aerosol100% (some euthanized with severe disease)16–21Hemorrhagic, facial edema, anorexia, tremor, and photophobia (one animal) [97, 137140]
Calomys callosus Unknown100–10,000 PFUi.p.0%NAPersistent infection model
Higher challenge doses favor clearance of virus
[96, 141]
GTOVGuinea pig/Hartley955511,000 PFUi.p.100%12–18Weight loss, hemorrhage[98]
Guinea pig/Strain 13955511,000 PFUi.p.100%12–18Weight loss, hemorrhage[98, 99]
PICVHamster/LVA
(Syrian golden; outbred)
AN 3739, AN 4763 35–3.5 × 106 PFUi.p., s.c.Lethality only in <8-day-old animals unless immunosuppressed6–35 in <8-day-old hamsters
7–18 immunosuppressed adult animals
Humoral response, adults clear virus[142, 143]
Hamster/MHA
(inbred)
AN 373935 PFU– PFUi.p.>70% lethality8–22Peak viremia day 8, higher challenge dose led to >90% lethality, and humoral response[142]
Guinea pig/strain 13AN 47630.003–3000 PFUs.c.0–100%13–18P18 virus lethal, P2 not lethal[144]
Guinea pig/HartleyAN 47630.003–3000 PFUs.c.0%–43%8–18Only high doses lethal[144]