Abstract
Despite flaviviruses remaining the leading cause of systemic human infections worldwide, ocular manifestations of these mosquito-transmitted viruses are considered relatively uncommon in part due to under-reporting. However, recent outbreaks of Zika virus (ZIKV) implicated in causing multiple ocular abnormalities, such as conjunctivitis, retinal hemorrhages, chorioretinal atrophy, posterior uveitis, optic neuritis, and maculopathies, has rejuvenated a significant interest in understanding the pathogenesis of flaviviruses, including ZIKV, in the eye. In this review, first, we summarize the current knowledge of the major flaviviruses (Dengue, West Nile, Yellow Fever, and Japanese Encephalitis) reported to cause ocular manifestations in humans with emphasis on recent ZIKV outbreaks. Second, being an immune privilege organ, the eye is protected from systemic infections by the presence of blood-retinal barriers (BRB). Hence, we discuss how flaviviruses modulate retinal innate response and breach the protective BRB to cause ocular or retinal pathology. Finally, we describe recently identified infection signatures of ZIKV and discuss whether these system biology-predicted genes or signaling pathways (e.g., cellular metabolism) could contribute to the pathogenesis of ocular manifestations and assist in the development of ocular antiviral therapies against ZIKV and other flaviviruses.
Highlights
Flaviviruses consist of more than 90 RNA-enveloped viruses out of which 30 can cause severe disease in humans and animals
There are two models proposed for the infection and entry of Zika virus (ZIKV) into the eye: (a) cell death caused by ZIKV infection in the outer blood-retinal barrier (BRB) might form the portal of entry of the virus into the eye and infect the inner layers, thereby causing inflammation and vision loss in severe infected cases [94]; (b) ZIKV could possibly enter via the retinal arteries which leads to infection of the retinal endothelial cells and pericytes and the virus enters the outer BRB via the choroid capillaries [104]
Ocular complications caused by flaviviruses and other viruses will have long-term economic, psychological and health implications
Summary
Flaviviruses consist of more than 90 RNA-enveloped viruses out of which 30 can cause severe disease in humans and animals. We provide flavivirus infections in humans worldwide and elaborate on their main features, systemic complications, and ocular involvement These viruses have evolved specific mechanisms to. We provide an overview of ocular complications resulting from flavivirus counteract the antiviral response from the host and exploit various metabolic pathways to cause infections in humans worldwide and elaborate on their main systemic complications, and disease. Family of lipid-enveloped viruses with a single-stranded ~10.5 kb positiveeye and cause ophthalmic sense RNA genome They encode only ten proteins which exploit host machinery to complete their infectious replication cycles. The non-structural proteins are involved in viral genome replication, budding, and deploying the host cell machinery. Pre-membrane and seven non-structural proteins (NS1, NS2A, NS3, NS4A, NSB, and NS5)
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