1000/1000
Hot
Most Recent
Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flavivirus genus and is principally transmitted by Aedes aegypti mosquitoes. ZIKV infection often causes no or only mild symptoms, but it can also trigger severe consequences, including microcephaly in infants and Guillain-Barré syndrome, uveitis, and neurologic manifestations in adults. Since numerous studies have indicated that there are slightly different tissue-specific pathologies in each animal model of ZIKV, the distinct ZIKV tropism of a given animal model must be understood to enable effective vaccine development.
Animal Species | ZIKV Strain | Route of Administration |
Pathologic Features | Reference |
---|---|---|---|---|
Mouse | ||||
C57BL/6 | PRVABC59 | Intravenous | Fetal resorption, little or no viral RNA in placenta and fetal heads | [19] |
CD-1 | IBH 30656, PRVABC59, FS13025 |
Intrauterine | Placental dysfunction and inflammation, increased aborted fetus numbers, reduced neonatal brain and cortical thickness | [20] |
SJL | ZIKV-BR | Intravenous | Malformations of congenital brain, intrauterine growth restriction, upregulation of apoptosis-related genes | [23] |
ICR | GZ01 | Intra-ventricular | Fetal death, microcephaly | [22] |
Human STAT2 KI | ZIKV-Dak-MA | Subcutaneous | Viral RNA in placenta and fetal heads | [24] |
Ifnar1−/− | FSS13025 | Subcutaneous | Fetal resorption, reduced fetal weight and size | [34] |
A129 | PRVABC59 | Subcutaneous | Viral RNA in placenta, maternal brain, and fetal heads, reduced fetal weight | [26] |
AG129 | P6-740 | Subcutaneous | Viral RNA in placenta and fetal heads, decreased weight and head length | [25] |
Monkey | ||||
Rhesus macaque | PRVABC59 | Subcutaneous | Viral RNA in fetus, increased maternal-placental-fetal inflammatory response, placenta damage, reduced oxygen permeability of the placental villi | [28] |
Rhesus macaque | ZIKV-BR | Subcutaneous | Fetal neuropathology, neuroprogenitor apoptosis and gliosis, placental pathology | [29] |
Rhesus macaque | SPH 2015 | Intra-amniotic | Viral RNA in fetal and placental tissues, early death of fetus, fetal ZIKV neurotropism, neuropathology at the end of gestation | [30] |
Pigtail macaque | FSS13025 | Subcutaneous | Reduced growth of the fetal biparietal diameter and fetal brain lesions, viral RNA in fetal brain and placenta | [31] |
Pigtail macaque | FSS13025, ZIKV-BR |
Subcutaneous | Decreased fetal non-cortical brain volume, injury in ependymal epithelium with underlying gliosis, reduced late fetal neuronal progenitor cells in the subventricular zone | [32] |
Marmoset | SPH 2015 | Intramuscular | Fetal demise and abortion, increase of proinflammatory cytokines, fetal neurocellular disorganization, viral RNA in placenta and fetus | [33] |
Animal Species | ZIKV Strain | Route of Administration |
Pathologic Features | Reference |
---|---|---|---|---|
Female | ||||
C57BL/6 | FSS13025 | Intravaginal | Viral RNA in vagina until 4 dpi (local replication) | [35] |
Ifnar1−/−, Irf3−/−Irf7−/− | FSS13025 | Intravaginal | High viral RNA levels in vagina | [35] |
C57BL/6J (+ anti-Ifnar1 mAb) |
ZIKV-BR | Intravaginal | ZIKV in the vaginal lumen, cervix, ovaries, uterine horns | [37] |
C57BL/6, CD8−/−, TCRβδ−/− (+ anti-Ifnar1 mAb) |
Dakar 41525, PRVABC59, H/PF/2013 |
Subcutaneous | Viral replicates in ovary, increased inflammation in the ovary, acute oophoritis | [36] |
Rhesus macaque | SPH 2015 | Intravaginal | Viral RNA in female reproductive tract, increased cytokine levels in cervicovaginal lavage | [38] |
Rhesus macaque, Cynomolgus macaque |
Thai, Puerto Rican |
Subcutaneous | Viral RNA in female reproductive tissues | [39] |
Male | ||||
C57BL/6 (+ anti-Ifnar1 mAb) |
Dakar 41519, H/PF/2013 |
Subcutaneous | Viral RNA in the testis and epididymis, decreased testis size, low testosterone level, infected spermatogonia, degradation of seminiferous tubule | [45] |
Ifnar−/− | MEX2-81 | Subcutaneous | Viral RNA and antigen in the epididymal lumen, testicular atrophy, low testosterone level | [46] |
Ifnar−/− | SMGC-1 | Intraperitoneal | Atrophy of the reproductive tract, virus in testicles, increased inflammation in the testis and epididymis | [48] |
AG129 | PRVABC59 | Intraperitoneal | Viral RNA and virus in semen, increased inflammation in testis and epididymis | [49] |
AG129 | SL1602 | Intraperitoneal | Viral RNA in testis and epididymis, increased inflammation in testis | [47] |
Cynomolgus macaque | IBH30656, PRVABC59, FSS13025 |
Subcutaneous | Virus in the testis | [50] |
Animal Species | ZIKV Strain | Route of Administration |
Pathologic Features | Reference |
---|---|---|---|---|
Brain | ||||
C57BL/6 (+ anti-Ifnar1 Ab) |
Dakar 41525 | Subcutaneous, intraperitoneal |
Lesions in CNS, high viremia, decreased weight | [56] |
Human STAT2 KI | ZIKV-Dak-MA | Subcutaneous | Viral RNA in brain | [24] |
A129 | MP1751 | Subcutaneous | Lesions in brain, viral RNA in the brain | [57] |
AG129 | H/PF/2013 | Footpad, intraperitoneal |
Virus in brain, neurodegeneration, myofiber necrosis, inflammatory cell infiltration, pathology in brain | [58] |
AG129 | P6–740 | Subcutaneous | Viral load in the brain, limb weakness, paralysis, increased neurological signs including locomotor hyperactivity, tremor, and seizure | [59] |
AG129 | MR 766 | Intraperitoneal | Paralysis, neurodegeneration, acute encephalitis, viral antigen in brain and spinal cord | [60] |
Ifnar−/−, Irf3−/−Irf5−/−Ifr7−/− TKO |
H/PF/2013, MR766 |
Subcutaneous, intravenous, intraperitoneal |
Viral RNA in brain and spinal cord, increased neurological disease signs including hindlimb weakness and paralysis | [18] |
Eye | ||||
C57BL/6 | PRVABC59 | Subcutaneous | Chorioretinal lesions, induced local inflammation and cellular infiltration | [63] |
C57BL/6, ISG15−/− |
PRVABC59 | Intravitreal | Chorioretinal atrophy with RPE mottling, increased multiple inflammatory and antiviral response genes in the retina, severe chorioretinitis coinciding with retinal cell death and higher virus replication in ISG15−/− mice | [64] |
C57BL/6, Ifnar1−/− |
PRVABC59 | Anterior segment of eyes, intraperitoneal |
Increased intraocular pressure, chorioretinal atrophy, increased expression of inflammatory mediators, retinal ganglion cell death | [65] |
Lymph node | ||||
Rhesus macaque | PRVABC59, Brazil/ZKV/2015 |
Subcutaneous | Virus in lymph nodes in both paracortical regions, germinal centers, and cerebrospinal fluid, upregulation of proinflammatory and anti-apoptotic signaling pathways | [67] |
Rhesus monkeys | ZIKV-BR | Intravenous | Activation of lymphoid tissues | [69] |
Rhesus monkeys | PRVABC59 | Subcutaneous | Virus in multiple lymphoid tissues, viral RNA in lymphoid and joint/muscle tissues | [68] |
Pigtail macaque | Brazil_2015_MG | Subcutaneous | Increase of innate immune cells in blood, lymph nodes, and mucosal tissues, activation of monocytes in peripheral lymph nodes | [70] |
Olive baboon | H/PF/2013, PRVABC59 |
Vaginal deposition of ZIKV-infected semen | Viral RNA in lymph nodes | [71] |