Table 3.
Pathological mechanisms and manifestations of ZIKV infection.
| Primary Targets | Receptors | Mechanisms | Outcomes |
|---|---|---|---|
| Neural progenitor cells | AXL [99]. | Apoptosis of ZIKV-infected NPCs. Reduced proliferation of NPCs. Premature differentiation of NPCs [113,115]. | Microcephaly [115]. |
| Neural crest cells | AXL [100]. | ZIKV infection of NCCs during the developmental stages of the fetus causes abnormal migration, proliferation, and differentiation of NCCs [100,120]. The loss of NCCs associated with ZIKV infection can contribute to the disruption of the formation of the optic fissure, resulting in failure to close the optic fissure [86,120]. ZIKV infection of NCCs will result in abnormal proliferation and differentiation of cells required for the normal development of the cornea [121]. ZIKV infection of NCCs during the developmental stages of the fetus can lead to abnormal morphogenesis of the trabecular meshwork [100,122,123]. |
Microphthalmia [106,120,124,125]. Iris coloboma [7,84,120,126]. Corneal ectasia [83]. Congenital glaucoma [93,100,122,123]. |
| Mesenchymal stem cells | AXL [101]. | ZIKV infects mesenchymal stem cells, resulting in impaired proliferation and differentiation of cells required for the development of the crystalline lens [30,100,121,127,128]. | Congenital cataract [30,100,121,127,128]. |
| Placental endothelial cells and trophoblasts | TIM-1, AXL, TYRO3 [27]. | Destruction of ZIKV-infected placenta [129,130]. Compromised maternal-fetal interface [129,130]. |
Placental insufficiency causes restricted growth of the fetus and disruption of neurodevelopment of the fetus [129]. Facilitate access of ZIKV to the fetus [129,130]. |
| Blood retinal barrier cells (Retinal vascular endothelial cells and retinal pigment epithelial cells) | AXL, TYRO3, TIM-1, RIG-I/MDA5, TLR3 [20]. | ZIKV infected BRB cells induce inflammation that damages the BRB and facilitate influx of effector immune cells into the retina [131,132]. | Chorioretinitis, macular pigment mottling, chorioretinal atrophy, and maculopathy [131,132]. |
| Cornea epithelial cells | TLR3, RIG-I, MDA5 [133]. | ZIKV-infected corneal epithelium induces antiviral response and immune-mediated inflammation [133]. | Keratitis [133]. |
| Trabecular meshwork cells | RIG-I, TLR3 [134]. | ZIKV-infected trabecular meshwork cells secrete cytokines and chemokines that promote inflammation via the recruitment of effector immune cells such as Th1 cells to the trabecular meshwork [134]. | Trabeculitis [134]. |
| Conjunctival epithelial cells | RIG-I/MDA5, TLR3 [135]. | ZIKV-infected conjunctival epithelial cells induce an immune-mediated inflammatory response [135]. | Nonpurulent conjunctivitis [135]. |
| Iris pigment epithelium | TLR3 [136]. | Immune-mediated inflammation triggered in response to ZIKV-infected iris pigment epithelium. ZIKV-infected blood aqueous barrier (BAB) cells induce inflammation that damages the BAB and facilitate influx of effector immune cells into the anterior uvea. Influx of ZIKV-infected monocytes acting as Trojan horses [137,138,139]. |
Anterior uveitis with or without raised intraocular pressure [137,138,139]. |