The endothelial cells of the BBB and BRB cells can secrete matrix metalloproteinase-2 (MMP-2) and MMP-9 that are responsible for disrupting the impermeability function of BBB and BRB to facilitate access of infiltrating effector immune cells into the brain and retina, respectively [107]. that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8+T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as nonstructural protein 5, are involved in the evasion of the hosts immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus ability to cross both the bloodCbrain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the hosts immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection. receptors (type I IFN receptor), a type 2 cytokine receptor. Type I IFN receptors consist of interferon alpha receptor1 (IFNAR1) and IFNAR2 subunits that project into the cell to form a cytoplasmic domain associated with Janus activated kinases, such as tyrosine kinase 2 (TYK2) and Janus activated kinase 1 (JAK1) [42,43]. The binding of type I IFN to its cognate receptor results in a signal cascade that activates JAK1 and TYK2. The activated Janus activated kinases phosphorylate tyrosine residues on the cytoplasmic domain to provide a docking site for signal transducer and activator of transcription 1 (STAT1) and STAT2 proteins. STAT1 and STAT2 Mouse monoclonal to SND1/P100 proteins are recruited by the activated JAKs, and subsequently they undergo phosphorylation and dimerization. The phosphorylated STAT1 and STAT2 proteins dissociate from JAKs and bind to interferon regulatory factor 9 (IRF9) to form the STAT1CSTAT2CIFR9 complex, a trimolecular complex called interferon-stimulated gene factor 3 (ISGF3). ISGF3 translocates into the nucleus of the Mecamylamine Hydrochloride host cell, where it binds to IFN-stimulated response element (ISRE) on DNA to trigger the transcription of interferon-stimulated genes (ISG) that induce an antiviral response to control the ZIKV infection (Figure 3) [42,43]. Thus, the innate immune response against ZIKV results in increased expression of RIG-I, MDA5, and TLR3 [10]. TLR3 engages dsRNA intermediates to induce the activation of IRF3 and NFB, whereas RIG-I/MDA5 engages dsRNA intermediates to induce the activation of IRF3/7 and NFB [25]. This interaction yields type I IFN, IL-6, IL-12, tumor necrosis factor alpha (TNF), type III IFN, ISG, CXCL10, and CCL5 [10,25]. Open in a separate window Figure 3 IFN/ generates the antiviral response to control ZIKV infection. IFN: Interferon alpha; IFN: Interferon beta; IFNAR1: interferon alpha receptor 1; IFNAR2: interferon alpha receptor 2; TYK2: Tyrosine kinase 2; JAK1: Janus activated kinase 1; STAT1: signal transducer and activator of transcription 1; STAT2: signal transducer and activator of transcription 2; IRF9: interferon regulatory factor 9; ISG: Interferon-stimulated genes. ZIKV, like most members of the flaviviruses, evades host immune responses by interfering with molecules that mediate innate immunity. NS1, NS4, and NS4B inhibit the signaling pathway essential for the generation of IRF3 and IRF7. NS4 inhibit the activity of MAVS, whereas NS1 and NS4B inhibit the activity of TBK1 [24]. However, it has been reported that NS5 inhibits the generation of type 1 IFN by mediating the degradation of STAT2 [4]. NS1, NS4B, and NS2B are involved in the process of mediating the evasion of the immune system, which is accomplished by blocking the activation of type I IFN and expression of ISG [19]. Type 1 Mecamylamine Hydrochloride IFN induces an antiviral microenvironment to limit the spread of the virus, as well as activate NK cells that mediate cytolytic and noncytolytic antiviral immune responses. Mecamylamine Hydrochloride Perforin and granzyme secreted by activated NK cells induce the cytolysis of ZIKV infected cells. NK cells secrete type II IFN (IFN).
