Table 4.
Mouse models for ZIKV neuropathogenesis.
| Model strain | Age | Virus inoculation route/dosage | ZIKV strains | ZIKV detected | Pathologies | Ref. |
|---|---|---|---|---|---|---|
| Ifnar1-/- or Irf3−/−Irf5−/− Irf7−/− triple KO | 5–6 weeks | s.c. (footpad) or i.p. or i.v./1 × 103 FFU | H/PF/2013, MR 766 | Serum, spleen, brain, spinal cord, and testes | Hindlimb paralysis, hindlimb weakness, death | (76) |
| C57BL/6 treated with IFNAR1 antibody | 4–5 weeks | i.p. or s.c./1 × 103–106 PFU | strain DAK AR D 41525 | Spleen, liver, kidney, heart, brain, spinal cord | Neuronal death, astrogliosis, microgliosis, scattered necrotic cellular debris, inflammatory cell infiltrates | (77) |
| Pregnant CD1 | E10 | i.u. 1x106 TCID50 units/100uL | FSS13025, Paraiba 2015 (ZIKVBR), PRVABC59 | Trophoblast and endothelial cells in the placenta, and endothelial, microglial and NPCs in the fetal brain | Placental inflammation and dysfunction, reduced fetal viability, neuroinflammation and cortical thinning in neonatal brains | (78) |
| Pregnant SJL | E10-13 | i.v./2 × 102, 8 × 109, or 2 × 1011 PFU | Paraiba 2015 (ZIKVBR) | Fetal brain, kidney, liver, spleen | Apoptosis in neural tissue, IUGR, cortical malformations similar to microcephaly | (72) |
| Pregnant C57 | E13.5 | i.p./9 × 104 PFU | SZ01 | Serum, placenta, fetal brain | Reduction of the cortical NPCs in the fetal mice. | (13) |
| Reduced cavity of lateral ventricles and surface areas of the cortex. | ||||||
| Pregnant C57BL/6J or 129S1/SvImJ | E14.5 | i.c./1.7 × 103 TCID50 | MEX1-44 | N/A | Postnatal growth restriction and microcephaly with neuronal loss, cell cycle arrest and apoptosis of NPCs, dysregulation of genes associated with immune responses in the brains, abnormal vascular development, BBB leakage, microglial activation, astrogliosis | (73) |
| ICR | E13.5 | Lateral ventricle (injection of fetus)/650 PFU | SZ01 | Fetal brain | apoptosis and cell-cycle arrest of NPCs, deregulation of associated with immune response, apoptosis pathways and microcephaly in the brains, Smaller brain size with enlarged ventricles and a thinner CP and VZ/SVZ | (74) |
| Ifnar1+/− (IFNAR1-/- × C57BL/6) | E6.5 or E7.5 | s.c. (footpad)/1 × 103 PFU | H/PF/2013 | Placenta, fetal head and body, maternal serum, spleen and brain | placental and fetal brain apoptosis, fetal demise, IUGR | (79) |
| Ifnar1+/− (C57BL/6 treated with anti-Ifnar antibody [MAR1-5A3]) | E6.5 or E7.5 | s.c. (footpad)/1 × 103 PFU | H/PF/2013 | Placenta, fetal head and body, maternal serum, spleen and brain | IUGR | (79) |
Ifnar, interferon-α/β receptor; IFR, interferon regulatory factor; NPCs, neural progenitor cells; IUGR, intra-uterine growth restriction; TCID50, 50% median tissue culture infectious dose; PFU, plaque forming units; CP, cortical plate; VZ, ventricular zone; SVZ, subventricular zone; i.p., intraperitoneal; s.c., subcutaneous; i.v., intravenous; i.c., intracerebral; i.u., intrauterine.