Zika Virus Infection of Human Iris Pigment Epithelial Cells

Ryan, Feargal J.; Carr, Jillian M.; Furtado, João M.; Ma, Yuefang; Ashander, Liam M.; Simões, Milena; Oliver, Genevieve F.; Granado, Gustavo Bracho; Dawson, Abby C.; Michael, Michael; Appukuttan, Binoy; Lynn, David J.; Smith, Justine R.

doi:10.3389/fimmu.2021.644153

Cited by 11 publications

(10 citation statements)

References 77 publications

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“…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].…”

Section: Primary Targets Receptors Mechanisms Outcomesmentioning

confidence: 99%

“…ZIKV-infected corneal epithelial cells express TLR3, RIG-I, and MDA5 to facilitate the generation of type I and III interferons that mediate antiviral response [133,137]. Singh and coworkers [133] demonstrated that ZIKV-infected corneal epithelial cells support ZIKV replication as well as promote ZIKV persistence in the cornea.…”

Section: Corneamentioning

confidence: 99%

“…Th1 cells recruited to the infected tissue secrete TNFα and IFNγ, which promote the cytokine-mediated inflammation of the infected tissue. CD8+T cells secrete perforin and granzyme that induce the direct cytotoxic destruction of ZIKV-infected cells [137,138]. Iris pigment epithelial cells express TLR3 [136].…”

Section: Conjunctivamentioning

confidence: 99%

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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: Primary Targets Receptors Mechanisms Outcomesmentioning

confidence: 99%

Section: Corneamentioning

confidence: 99%

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Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

Labib

Chigbu

2022

TropicalMed

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“…The expression of IRF2 including IRF1 binding site at promoter region is inducible by transient or stable IRF1 expression [ 32 – 34 ]. IRF2 was up-regulated in ZIKV infection of human iris pigment epithelial cells [ 35 ]. In another study, IRF2 expression was induced during acute and latent infection [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3

Ren

Zhu

Sun

et al. 2021

Virol J

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Background Although interferon regulatory factor 2 (IRF2) was reported to stimulate virus replication by suppressing the type I interferon signaling pathway, because cell cycle arrest was found to promote viral replication, IRF2-regulated replication fork factor (FAM111A and RFC3) might be able to affect ZIKV replication. In this study, we aimed to investigate the function of IRF2, FAM111A and RFC3 to ZIKV replication and underlying mechanism. Methods siIRF2, siFAM111A, siRFC3 and pIRF2 in ZIKV-infected A549, 2FTGH and U5A cells were used to explore the mechanism of IRF2 to inhibit ZIKV replication. In addition, their expression was analyzed by RT-qPCR and western blots, respectively. Results In this study, we found IRF2 expression was increased in ZIKV-infected A549 cells and IRF2 inhibited ZIKV replication independent of type I IFN signaling pathway. IRF2 could activate FAM111A expression and then enhanced the host restriction effect of RFC3 to inhibit replication of ZIKV. Conclusions We speculated the type I interferon signaling pathway might not play a leading role in regulating ZIKV replication in IRF2-silenced cells. We found IRF2 was able to upregulate FAM111A expression and thus enhance the host restriction effect of RFC3 on ZIKV.

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“…The ARPE-19 human retinal epithelial cell line exhibits differences from primary human cells, including in the setting of infection [30]. Also, there are differences in gene expression between individuals that may be considerable [30,36,37]. Therefore, we sought to confirm the key finding of a difference in infectivity and host response between DENV-1 strains from the 2005 versus the 2007 Singapore epidemics using retinal pigment epithelial cells individually isolated from eyes of five different human donors.…”

Section: Viral Load and Cell Response Are Different In Human Primary Retinal Pigment Epithelial Cells Infected With Different Dengue Virumentioning

confidence: 97%

Infection of Human Retinal Pigment Epithelial Cells with Dengue Virus Strains Isolated during Outbreaks in Singapore

et al. 2022

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Prevalence of dengue retinopathy varies across epidemics, with the disease linked to circulation of dengue virus serotype 1 (DENV-1). The retinal pigment epithelium has been implicated in the pathology. We investigated infectivity, molecular response, and barrier function of epithelial cells inoculated with DENV strains from different outbreaks in Singapore. Monolayers of human retinal pigment epithelial cells (multiple primary cell isolates and the ARPE-19 cell line) were inoculated with six DENV strains, at multiplicity of infection of 10; uninfected and recombinant strain-infected controls were included where relevant. Infectivity and cell response were assessed primarily by RT-qPCR on total cellular RNA, and barrier function was evaluated as electrical resistance across monolayers. Higher viral RNA loads were measured in human retinal pigment epithelial cells infected with DENV-1 strains from the 2005 Singapore epidemic, when retinopathy was prevalent, versus DENV-1 strains from the 2007 Singapore epidemic, when retinopathy was not observed. Type I interferon (IFN) transcripts (IFN-β and multiple IFN-stimulated genes) were up-regulated, and impact on barrier function was more pronounced, for cells infected with DENV-1 strains from the 2005 versus the 2007 Singapore epidemics. Aside from serotype, strain of DENV may determine the potential to induce retinal pathology. Identification of molecular markers of disease-associated DENV strains may provide insights into the pathogenesis of dengue retinopathy.

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Zika Virus Infection of Human Iris Pigment Epithelial Cells

Cited by 11 publications

References 77 publications

Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases

IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3

Infection of Human Retinal Pigment Epithelial Cells with Dengue Virus Strains Isolated during Outbreaks in Singapore

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