Vero Cell Proteomic Changes Induced by Zika Virus Infection

Glover, Kathleen K. M.; Gao, Ang; Zahedi-Amiri, Ali; Coombs, Kevin M.

doi:10.1002/pmic.201800309

Cited by 25 publications

(33 citation statements)

References 61 publications

(86 reference statements)

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“…Evidence indicating that ZIKV may interfere with IGF pathway gene expression has been described recently by Glover and colleagues 35 that showed activation of IGF1 pathway signaling in Vero cells after ZIKV infection. Primary human astrocytes infected with either African and Asian ZIKV strains secreted less IGF2 than levels secreted by the controls.…”

Section: Discussionmentioning

confidence: 81%

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

Suzukawa

Zanluca

Jorge³

et al. 2020

Journal of Infection

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Objectives: Screening for genes differentially expressed in placental tissues, aiming to identify transcriptional signatures that may be involved in ZIKV congenital pathogenesis. Methods: Transcriptome data from placental tissues of pregnant women naturally infected with Zika virus during the third trimester were compared to those from women who tested negative for Zika infection. The findings were validated using both a cell culture model and an immunohistochemistry/morphological analysis of naturally infected placental tissues. Results: Transcriptome analysis revealed that Zika virus infection induces downregulation of insulin-like growth factor II (IGF2) gene, an essential factor for fetal development. The Caco-2 cell culture model that constitutively expresses IGF2 was used for the transcriptome validation. Asiatic and African Zika virus strains infection caused downregulated IGF2 gene expression in Caco-2 cells, whereas other flaviviruses, such as dengue serotype 1, West Nile and wild-type yellow fever viruses, had no effect on this gene expression. Immunohistochemical assays on decidual tissues corroborated our transcriptome analysis, showing that IGF2 is reduced in the decidua of Zika virus-infected women. Conclusions: Our results draw attention to IGF2 modulation in uterine tissues, and this finding is expected to support future studies on strategies to ameliorate the harmful effects of Zika virus infection during pregnancy.

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Section: Discussionmentioning

confidence: 81%

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

Suzukawa

Zanluca

Jorge³

et al. 2020

Journal of Infection

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“…A total of 446 host proteins were significantly dysregulated at any time point, and 71 were dysregulated > 1.375-fold ( Table 1 ). The majority of dysregulated proteins were significantly upregulated at 12 hpi, irrespective of the fold-change cut-off used ( Table 1 ), a pattern that was not reflected by our previous analyses of ZIKV-infected Vero [ 15 ], U-251 astrocytoma [ 16 ] or Sertoli cells [ 17 ]. Bioinformatic analysis using Ingenuity Pathway analysis (IPA) predicted several pathways that were activated and inhibited by ZIKV infection.…”

Section: Introductionmentioning

confidence: 80%

ZIKV Infection Induces DNA Damage Response and Alters the Proteome of Gastrointestinal Cells

Glover

Coombs

2020

Viruses

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The zika virus (ZIKV) is a neurotropic virus that causes congenital abnormalities in babies when they are infected in utero. Some studies have reported these congenital abnormalities result from ZIKV attacking neural progenitor cells within the brain which differentiate into neurons, oligodendrocytes, and astrocytes. Each of these glial cells play important roles during development of the fetal brain. In addition to ZIKV-induced congenital abnormalities, infected patients experience gastrointestinal complications. There are presently no reports investigating the role of this virus at the proteomic level in gastrointestinal associated cells, so we conducted an in vitro proteomic study of ZIKV-induced changes in Caco-2, a colon-derived human cell line which is known to be permissive to ZIKV infection. We used SomaScan, a new aptamer-based proteomic tool to identify host proteins that are dysregulated during ZIKV infection at 12, 24, and 48 h post-infection. Bioinformatic analyses predicted that dysregulation of differentially-regulated host proteins results in various gastrointestinal diseases. Validation of the clinical relevance of these promising protein targets will add to the existing knowledge of ZIKV biology. These potential proteins may be useful targets towards the development of therapeutic interventions.

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“…Protein concentrations of BCA-determined cell lysates were adjusted to 200 ng/µL, and 70 µL of each sample submitted for SOMAscan ® analysis in-house on a SomaLogics ® -licensed platform in the Manitoba Centre for Proteomics and Systems Biology as described [17,23,24]. Briefly, the SOMAscan assay is a novel proteomic tool that uses single-stranded DNA-based Slow Off-rate Modified Aptamer reagents (SOMAmers).…”

Section: Somascan ® Analysesmentioning

confidence: 99%

“…Fold-changes were determined for each of the six treated samples compared to their time-matched non-treated samples. The fold-changes were analyzed for significance by both Students t-test with 2 tails, and by Z-score analysis, as described [23,25]. Briefly, all fold-changes not deemed to be significant by t-test were examined by Z-score, expressing each value as its number of standard deviations away from the population mean.…”

Section: Statistical and Bioinformatic Analysesmentioning

confidence: 99%

Autophagy Modulators Profoundly Alter the Astrocyte Cellular Proteome

Sher

Gao

Coombs

2020

Cells

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Autophagy is a key cellular process that involves constituent degradation and recycling during cellular development and homeostasis. Autophagy also plays key roles in antimicrobial host defense and numerous pathogenic organisms have developed strategies to take advantage of and/or modulate cellular autophagy. Several pharmacologic compounds, such as BafilomycinA1, an autophagy inducer, and Rapamycin, an autophagy inhibitor, have been used to modulate autophagy, and their effects upon notable autophagy markers, such as LC3 protein lipidation and Sequestosome-1/p62 alterations are well defined. We sought to understand whether such autophagy modulators have a more global effect upon host cells and used a recently developed aptamer-based proteomic platform (SOMAscan®) to examine 1305 U-251 astrocytic cell proteins after the cells were treated with each compound. These analyses, and complementary cytokine array analyses of culture supernatants after drug treatment, revealed substantial perturbations in the U-251 astrocyte cellular proteome. Several proteins, including cathepsins, which have a role in autophagy, were differentially dysregulated by the two drugs as might be expected. Many proteins, not previously known to be involved in autophagy, were significantly dysregulated by the compounds, and several, including lactadherin and granulins, were up-regulated by both drugs. These data indicate that these two compounds, routinely used to help dissect cellular autophagy, have much more profound effects upon cellular proteins.

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Vero Cell Proteomic Changes Induced by Zika Virus Infection

Cited by 25 publications

References 61 publications

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

ZIKV Infection Induces DNA Damage Response and Alters the Proteome of Gastrointestinal Cells

Autophagy Modulators Profoundly Alter the Astrocyte Cellular Proteome

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