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KMID : 0381120220440121499
Genes and Genomics
2022 Volume.44 No. 12 p.1499 ~ p.1507
Transcriptional induction of TGF-¥â1 and endothelial-to-mesenchymal transition cell markers in human umbilical vein endothelial cells by Ebola virus infection
Ro Young-Tae

Patterson Jean L
Abstract
Background: Ebola virus (EBOV) causes a serious hemorrhagic disease in humans, with a mortality rate of up to 80%. Despite significant achievements in the past decades elucidating the pathogenesis of EBOV, there is still much to be elucidated about the cell type-specific host response and their functional roles during infection.

Objective: This study aimed to gain insight into cell type-specific host responses to EBOV infection.

Methods: Real-time RT-qPCR analysis was used to identify host transcriptional changes in epithelial Caco-2 cells and endothelial HUVECs by EBOV infection.

Results: EBOV efficiently infected to both Caco-2 cells and HUVECs, depending on the time of infection. However, changes in the transcriptional levels of several host cellular genes following viral infection showed significant differences between Caco-2 cells and HUVECs. EBOV infection increases the transcription of TGF-¥â1, a key factor in epithelium-to-mesenchyme transition (EMT), only in HUVECs, but not in Caco-2 cells. This upregulation in turn induces the transcription of other EMT signaling molecules such as snail, slug and MMP9, ultimately leading to endothelial-to-mesenchymal transition (EndMT). Furthermore, this EndMT process appears to be associated with increased transcription of stem-cell markers such as Klf4, Sox2 and Oct4. However, most of these transcriptional changes due to EBOV infection did not occur in Caco-2 cells, suggesting that EMT or EndMT by EBOV infection is cell type-specific.

Conclusion: We propose that EBOV infection induces the expression of TGF-¥â1-mediated signals in endothelial HUVECs, resulting in EndMT. This could provide broader information to elucidate the pathogenesis of Ebola virus disease.
KEYWORD
Ebola virus, Endothelial-to-mesenchymal transition (EndMT), RT-qPCR, TGF-¥â1 signaling, Transcriptiona1 analysis.
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