Zika Virus Efficiently Replicates in Human Retinal Epithelium and Disturbs Its Permeability

Salinas, Sara; Erkilic, Nejla; Damodar, Krishna; Molès, Jeàn-Pierre; Fournier‐Wirth, Chantal; Perre, Philippe Van de; Kalatzis, Vasiliki; Simonin, Yannick

doi:10.1128/jvi.02144-16

Cited by 23 publications

(19 citation statements)

References 16 publications

(1 reference statement)

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“…We reported that ZIKV causes chorioretinal atrophy in an experimental mouse models, and that cells lining the blood-retinal barrier (BRB) are permissive to ZIKV infection [27]. Consistent with our findings, several independent studies also demonstrated the permissive nature of BRB cells to ZIKV infection [32][33][34][35]. How ZIKV modulates the BRB to gain access to the eye remains an active area of investigation in our lab [25].…”

Section: Introductionsupporting

confidence: 85%

Interferon-stimulated gene 15 (ISG15) restricts Zika virus replication in primary human corneal epithelial cells

Singh

Farr

et al. 2019

The Ocular Surface

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Purpose: Zika virus (ZIKV) has emerged as an important human pathogen causing ocular complications. There have been reports of the shedding of ZIKV in human as well as animal tears. In this study, we investigated the infectivity of ZIKV in corneal epithelial cells and their antiviral immune response. Methods: Primary human corneal epithelial cells (Pr. HCECs) and an immortalized cell line (HUCL) were infected with two different strains of ZIKV (PRVABC59 & BeH823339) or dengue virus (DENV, serotypes 1-4). Viral infectivity was assessed by immunostaining of viral antigen and plaque assay. qRT-PCR and immunoblot analyses were used to assess the expression of innate inflammatory and antiviral genes. Supplementation of recombinant ISG15 (rISG15) and gene silencing approaches were used to elucidate the role of ISG15 in corneal antiviral defense. Results: Pr. HCECs, but not the HUCL cells, were permissive to both ZIKV strains and specifically to DENV3 infection. ZIKV induced the expression of viral recognition receptors (TLR3, RIG-I, & MDA5), and genes involved in inflammatory (CXCL10& CCL5) and antiviral (IFNs, MX1, OAS2, ISG15) responses in Pr. HCECs. Furthermore, ZIKV infection caused Pr. HCECs cell death, as evidenced by TUNEL staining. Silencing of ISG15 increased ZIKV infectivity while supplementation with rISG15 reduced ZIKV infection by direct inactivation of ZIKV and inhibiting its entry. Conclusions: Our study demonstrates for the first time, that ZIKV virus can readily infect and replicate in Pr. HCECs. Therefore, ZIKV may persist in the cornea and pose the potential risk of transmission via corneal transplantation.

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Section: Introductionsupporting

confidence: 85%

Interferon-stimulated gene 15 (ISG15) restricts Zika virus replication in primary human corneal epithelial cells

Singh

Farr

et al. 2019

The Ocular Surface

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“…Zhao et al and Aleman et al have independently shown the Muller glia cells to be the primary target of ZIKV infection leading to decreased neurotropic functions and increased pro-inflammatory cytokines post infection with the help of murine models [ 96 , 98 ]. ZIKV infection in RPE was shown to disrupt its cell to cell adhesion and barrier properties [ 99 ]. Similarly, ZIKV was found to infect human fetal retinal pigment epithelial cells (FRPE), iPSC-derived retinal stem cells (iRSCs), and retinal cup (RC) organoids [ 100 ].…”

Section: Experimental Models Of Ocular Zikv Complicationsmentioning

confidence: 99%

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier

Singh

Kumar

2018

Viruses

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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.

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“…ZIKV has a tropism for many human cells and tissues [ 43 ]. It can infect the skin fibroblasts, keratinocytes and dendritic cells [ 22 ], monocytes [ 44 , 45 ], retinal epithelium [ 46 ], brain cells including neural progenitors, neurons, astrocytes and glial cells [ 23 , 41 , 47 , 48 ], uterine fibroblasts [ 49 ], placental cells [ 50 ] and testicular cells [ 51 , 52 ]. In cell culture, insect C6/36 and monkey epithelial Vero cell lines have been widely used to amplify ZIKV [ 30 , 53 ], whereas human fibroblasts MRC-5, hepatic Huh7, lung epithelial cells A549, astrocytic U251MG, neuronal stem cells and neuroblastoma SK-N-SH and SH-SY5Y cell lines are permissive for ZIKV infection [ 40 , 53 , 54 , 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Higher Cytopathic Effects of a Zika Virus Brazilian Isolate from Bahia Compared to a Canadian-Imported Thai Strain

Alpuche-Lazcano

McCullogh

Corpo

et al. 2018

Viruses

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Zika virus (ZIKV) is an emerging pathogen from the Flaviviridae family. It represents a significant threat to global health due to its neurological and fetal pathogenesis (including microcephaly and congenital malformations), and its rapid dissemination across Latin America in recent years. The virus has spread from Africa to Asia, the Pacific islands and the Americas with limited knowledge about the pathogenesis associated with infection in recent years. Herein, we compared the ability of the Canadian-imported Thai strain PLCal_ZV and the Brazilian isolate HS-2015-BA-01 from Bahia to produce infectious ZIKV particles and cytopathic effects in a cell proliferation assay. We also compared the intracellular viral RNA accumulation of the two strains by quantitative RT-PCR (reverse transcription polymerase chain reaction) analyses. Our observations show that HS-2015-BA-01 is more cytopathic than PLCal_ZV in proliferation assays in Vero, Human Embryonic Kidney HEK 293T and neuroblastoma SH-SY5Y cells. Quantitative RT-PCR shows that the level of viral RNA is higher with HS-2015-BA-01 than with PLCal_ZV in two cell lines, but similar in a neuroblastoma cell line. The two strains have 13 amino acids polymorphisms and we analyzed their predicted protein secondary structure. The increased cytopathicity and RNA accumulation of the Brazilian ZIKV isolate compared to the Thai isolate could contribute to the increased pathogenicity observed during the Brazilian epidemic.

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Zika Virus Efficiently Replicates in Human Retinal Epithelium and Disturbs Its Permeability

Cited by 23 publications

References 16 publications

Interferon-stimulated gene 15 (ISG15) restricts Zika virus replication in primary human corneal epithelial cells

Interferon-stimulated gene 15 (ISG15) restricts Zika virus replication in primary human corneal epithelial cells

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier

Higher Cytopathic Effects of a Zika Virus Brazilian Isolate from Bahia Compared to a Canadian-Imported Thai Strain

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