Association of Anterior Uveitis With Acute Zika Virus Infection in Adults

Troumani, Y.; Touhami, Sara; Jackson, Timothy L.; Ventura, Camila V.; Stanescu-Segall, Dinu; Errera, Marie‐Hélène; Rousset, Dominique; Bodaghi, Bahram; Cartry, Guilhem; David, Thierry; Beral, L.

doi:10.1001/jamaophthalmol.2020.5131

Cited by 16 publications

(10 citation statements)

References 25 publications

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“…In acute ZIKV infection, there is no definitive outline of symptoms. They vary from anterior segment findings of conjunctivitis and anterior uveitis to posterior segment findings of maculopathy with outer retinal layer and retinal pigment epithelium (RPE) disruption (Table 1) [8,[57][58][59][60][61]. The most common ocular manifestation in acute ZIKV infection is a nonpurulent conjunctivitis, arising in up to 63% of patients [62].…”

Section: Ocular Manifestationsmentioning

confidence: 99%

Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

Labib

Chigbu

2022

TropicalMed

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Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain–Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells 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 non-structural protein 5, are involved in the evasion of the host’s immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus’ ability to cross both the blood–brain 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 host’s immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection.

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Section: Ocular Manifestationsmentioning

confidence: 99%

Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

Labib

Chigbu

2022

TropicalMed

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“…Zika virus disease is often asymptomatic or manifest as a mild and self-limited systemic illness in adult patients. However, serious inflammatory complications may occur, and these include anterior uveitis, which has been linked with presence of ZIKV in the anterior eye (8,9). Our work represents the first research to examine mechanisms of Zika-associated anterior uveitis, focusing on the interactions between the virus and iris pigment epithelial cells, and using the PRVABC59 strain isolated during the American epidemic and primary cells isolated within 24 hours of death from human cadaveric donors.…”

Section: Discussionmentioning

confidence: 99%

“…Different types of uveitis have been reported in adult patients infected with ZIKV (7). The most common form is anterior uveitis -based in the iris and ciliary body-which occurs in approximately 50% of patients who present with "red eyes" in the context of Zika fever (8). This uveitis is typically bilateral, may impact the visual acuity, and often is accompanied by an elevation of intraocular pressure, as we (9) and others (8,10,11) have documented (Table 1).…”

Section: Introductionmentioning

confidence: 94%

“…The most common form is anterior uveitis -based in the iris and ciliary body-which occurs in approximately 50% of patients who present with "red eyes" in the context of Zika fever (8). This uveitis is typically bilateral, may impact the visual acuity, and often is accompanied by an elevation of intraocular pressure, as we (9) and others (8,10,11) have documented (Table 1). In one of the first reports of Zika-associated anterior uveitis, aqueous humor was collected from the eye of a patient treated with corticosteroid eye drops alone; ZIKV RNA was recovered from fluid taken at 8 days after the onset of systemic symptoms, but not at 16 days (9).…”

Section: Introductionmentioning

confidence: 98%

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Zika Virus Infection of Human Iris Pigment Epithelial Cells

et al. 2021

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During recent Zika epidemics, adults infected with Zika virus (ZIKV) have developed organ-specific inflammatory complications. The most serious Zika-associated inflammatory eye disease is uveitis, which is commonly anterior in type, affecting both eyes and responding to corticosteroid eye drops. Mechanisms of Zika-associated anterior uveitis are unknown, but ZIKV has been identified in the aqueous humor of affected individuals. The iris pigment epithelium is a target cell population in viral anterior uveitis, and it acts to maintain immune privilege within the anterior eye. Interactions between ZIKV and human iris pigment epithelial cells were investigated with infectivity assays and RNA-sequencing. Primary cell isolates were prepared from eyes of 20 cadaveric donors, and infected for 24 hours with PRVABC59 strain ZIKV or incubated uninfected as control. Cytoimmunofluorescence, RT-qPCR on total cellular RNA, and focus-forming assays of culture supernatant showed cell isolates were permissive to infection, and supported replication and release of infectious ZIKV. To explore molecular responses of cell isolates to ZIKV infection at the whole transcriptome level, RNA was sequenced on the Illumina NextSeq 500 platform, and results were aligned to the human GRCh38 genome. Multidimensional scaling showed clear separation between transcriptomes of infected and uninfected cell isolates. Differential expression analysis indicated a vigorous molecular response of the cell to ZIKV: 7,935 genes were differentially expressed between ZIKV-infected and uninfected cells (FDR < 0.05), and 99% of 613 genes that changed at least two-fold were up-regulated. Reactome and KEGG pathway and Gene Ontology enrichment analyses indicated strong activation of viral recognition and defense, in addition to biosynthesis processes. A CHAT network included 6275 molecular nodes and 24 contextual hubs in the cell response to ZIKV infection. Receptor-interacting serine/threonine kinase 1 (RIPK1) was the most significantly connected contextual hub. Correlation of gene expression with read counts assigned to the ZIKV genome identified a negative correlation between interferon signaling and viral load across isolates. This work represents the first investigation of mechanisms of Zika-associated anterior uveitis using an in vitro human cell model. The results suggest the iris pigment epithelium mounts a molecular response that limits intraocular pathology in most individuals.

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“…As the clinical entities associated with ZIKV infection become clearer with time, there is a need for a shift toward more basic understanding of the virus and the pathogenic processes in the eye. The study by Troumani et al 4 provides insight as to how ZIKV-associated uveitis can progress with time. Well-designed clinical and mechanistic studies are needed to better understand the prevalence and pathophysiology of this disease entity.…”

mentioning

confidence: 99%