Persistence of Zika virus in conjunctival fluid of convalescence patients

Tan, Jeslin J. L.; Balne, Praveen Kumar; Leo, Yee Sin; Tong, Louis; Ng, Lisa F. P.; Agrawal, Rupesh

doi:10.1038/s41598-017-09479-5

Cited by 46 publications

(33 citation statements)

References 38 publications

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“…Although the reported cases of African lineage infections were too few to identify similar symptomatology, ocular infections by the Asian lineage have been documented in humans and recapitulated in animal models. Inner retinal vasculopathy ( 79 ) or other ocular infections have been reported linked to international travel into South American and Caribbean island nations ( 79 , 80 ). Ocular abnormalities have been documented in infants with congenital Zika virus syndrome (CZS).…”

Section: Zikv Transmission and Tissue Tropismmentioning

confidence: 99%

Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development

et al. 2018

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Zika virus (ZIKV) became a public health emergency of global concern in 2015 due to its rapid expansion from French Polynesia to Brazil, spreading quickly throughout the Americas. Its unexpected correlation to neurological impairments and defects, now known as congenital Zika syndrome, brought on an urgency to characterize the pathology and develop safe, effective vaccines. ZIKV genetic analyses have identified two major lineages, Asian and African, which have undergone substantial changes during the past 50 years. Although ZIKV infections have been circulating throughout Africa and Asia for the later part of the 20th century, the symptoms were mild and not associated with serious pathology until now. ZIKV evolution also took the form of novel modes of transmission, including maternal–fetal transmission, sexual transmission, and transmission through the eye. The African and Asian lineages have demonstrated differential pathogenesis and molecular responses in vitro and in vivo. The limited number of human infections prior to the 21st century restricted ZIKV research to in vitro studies, but current animal studies utilize mice deficient in type I interferon (IFN) signaling in order to invoke enhanced viral pathogenesis. This review examines ZIKV strain differences from an evolutionary perspective, discussing how these differentially impact pathogenesis via host immune responses that modulate IFN signaling, and how these differential effects dictate the future of ZIKV vaccine candidates.

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Section: Zikv Transmission and Tissue Tropismmentioning

confidence: 99%

Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development

et al. 2018

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“…Due to zika virus neurotropism for infect neural cells in human embryonic development, the ocular cells obtained in this study may represent an adequate model for analysis of molecular alterations resulting from ZIKV virus and neuronal cells interaction. Moreover, since viral ZIKV RNA may be present in ocular fluids (in tears and lacrimal glands) 49, 50, 51 , in our study we provide a methodology for cell capture with different perspectives of application. For example, the technique is applicable to the immunolocalization of a wide range of proteins, including detection of ZIKV antigens; to viral analysis through Real Time PCR and ultrastructural microscopy.…”

Section: Discussionmentioning

confidence: 99%

Impression cytology is a non-invasive and effective method for ocular cell obtention from babies with Congenital Zika Syndrome: perspectives in OMIC studies

Barbosa

Santos

Silva

et al. 2019

Preprint

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IMPORTANCENoninvasive techniques for obtaining ocular surface cells (neuroepithelial) from babies with Congenital Zika Syndrome CZS - resulting from infection by zika virus (ZIKV) during gestational period (malformations include ocular abnormalities and microcephaly) - remain to be determined.OBJECTIVESThe aim of this study was to describe an optimized impression cytology method for the isolation of viable cells from babies with CZS in satisfactory amounts and quality to enable the application in the context of genome approaches well as morphological and molecular evaluations.DESIGN, SETTINGS AND PARTICIPANTSIn this observational study, ocular surface samples were obtained with a hydrophilic nitrocellulose membrane (through optimized impression cytology method) from twelve babies referred to the Pediatric Service of the Antonio Pedro Hospital, Universidade Federal Fluminense (UFF), Niteroi, Rio de Janeiro, Brazil. Samples were collected with an authorized informed consent from both eyes of eight ZIKV infected babies according to the CZS diagnostic criteria (4 babies with positive PCR for Zika virus in gestation and presence of clinical signs which included ocular abnormalities and microcephaly and 4 babies with positive PCR for Zika virus during gestation but no clinical signs identified) and four unaffected babies (control samples / negative PCR, without clinical signs). Cells were used for microscopy analyses, transcriptomic and proteomic experiments and molecular procedure.MAIN OUTCOMES AND MEASURESThe microscopic features of the conjunctival epithelial cells were described by both direct analysis of the membrane-attached cells and analysis of cytospinned captured cells using several staining procedures, including viability evaluation. In parallel, molecular approaches were performed.RESULTSOn impression cytology, a considerable amount of viable cells were captured. Epithelial basal, polyhedral and goblet cells were clearly identified in all groups. All cases of ZIKV infected babies showed clear morphological alterations (cell keratinization, piknosis, karyolysis, anucleation and vacuolization). Genomic DNA and RNA were successfully isolated from all samples and allowed the establishment of transcriptomic and proteomic studies. Transcriptome analysis showed 8582 transcripts quantified in all samples and 63 differentially expressed genes in ocular cells from the exposed babies. Proteomics analysis allowed the identification of 2080, 2085 and 2086 high confident and unique proteins with at least one unique peptide in the unaffected, exposed to ZIKV and asymptomatic and CZS babies, respectively, being 2062 in common. Multivariate supervised analysis using the total quantitative protein features revealed a clear discrimination between the groups.CONCLUSIONS AND RELEVANCEOur method proved to be a suitable, fast, and non-invasive tool for detailed and precise morphological analyses with a perspective of application in OMIC studies for clinical and research studies of CZS.Key pointsQuestionAre the ocular surface cells of babies with Congenital Zika Syndrome viable to investigate the association between Zika virus infection during embryogenesis and ocular impairment?FindingsTo this date, this is the first study using an approach with perspectives in morphological, molecular and “OMICs” research from ocular samples captured by impression cytology of ZIKV infected babies during embryogenesis. The microscopic features of the conjunctival epithelial cells from all ZIKV infected babies showed clear morphological alterations.MeaningOcular cell surface capture offers a powerful model for studying the pathways involved in ocular diseases associated with ZIKV.

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“…Hence, RT-PCR has an advantage over serology due to its specificity. Additionally, ZIKV RNA detection by RT-PCR is an indication of acute ZIKV infection, although persistence has been observed in urine, saliva, tears and semen 25 , 31 , 35 – 37 .…”

Section: Discussionmentioning

confidence: 99%

Efficient detection of Zika virus RNA in patients’ blood from the 2016 outbreak in Campinas, Brazil

Judice

Tan

Parise³

et al. 2018

Sci Rep

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Infection with Zika virus (ZIKV), a mosquito-borne flavivirus has been casually linked with increased congenital microcephaly in Brazil from 2015 through 2016. Sensitive and specific diagnosis of patients with Zika fever (ZIKF) remains critical for patient management. We developed a ZIKV NS5 qRT-PCR assay by combining primers described by Balm et al. and a new Taqman probe. The assay was evaluated and compared with another assay described by Lanciotti et al. (ZIKV 1107) using 51 blood and 42 urine samples from 54 suspected ZIKV patients. ZIKV NS5 performed better in terms of sensitivity with more samples detected as ZIKV-positive (n = 37) than ZIKV 1107 (n = 34) for urine, and ZIKV-positive (n = 29) than ZIKV 1107 (n = 26) for blood. Both assays displayed good overall agreement for urine (κappa = 0.770) and blood (κappa = 0.825) samples. Improved availability of validated diagnostic tests, such ZIKV NS5 qRT-PCR, will be critical to ensure adequate and accurate ZIKV diagnosis.

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Persistence of Zika virus in conjunctival fluid of convalescence patients

Cited by 46 publications

References 38 publications

Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development

Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development

Impression cytology is a non-invasive and effective method for ocular cell obtention from babies with Congenital Zika Syndrome: perspectives in OMIC studies

Efficient detection of Zika virus RNA in patients’ blood from the 2016 outbreak in Campinas, Brazil

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