TGF-β1 Promotes Zika Virus Infection in Immortalized Human First-Trimester Trophoblasts via the Smad Pathway

Quang Duy Trinh, Ngan Thi Kim Pham, Kazuhide Takada, Chika Takano, Shihoko Komine-Aizawa, Satoshi Hayakawa

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The Zika virus (ZIKV) is well known for causing congenital Zika syndrome if the infection occurs during pregnancy; however, the mechanism by which the virus infects and crosses the placenta barrier has not been completely understood. In pregnancy, TGF-β1 is abundant at the maternal–fetal interface. TGF-β1 has been reported to enhance rubella virus binding and infection in human lung epithelial cells. Therefore, in this study, we investigate the role of TGF-β1 in ZIKV infection in the immortalized human first-trimester trophoblasts, i.e., Swan.71. The cells were treated with TGF-β1 (10 ng/mL) for two days before being inoculated with the virus (American strain PRVABC59) at a multiplicity of infection of five. The results showed an enhancement of ZIKV infection, as demonstrated by the immunofluorescent assay and flow cytometry analysis. Such enhanced infection effects were abolished using SB431542 or SB525334, inhibitors of the TGF-β/Smad signaling pathway. An approximately 2-fold increase in the virus binding to the studied trophoblasts was found. In the presence of the Smad inhibitors, virus replication was significantly suppressed. An enhancement in Tyro3 and AXL (receptors for ZIKV) expression induced by TGF-β1 was also noted. The results suggest that TGF-β1 promotes the virus infection via the Smad pathway. Further studies should be carried out to clarify the underlying mechanisms of these findings.

Original languageEnglish
Article number3026
JournalCells
Volume11
Issue number19
DOIs
Publication statusPublished - Oct 2022

Keywords

  • AXL
  • TGF-β1
  • Tyro3
  • Zika
  • congenital Zika syndrome
  • first trimester
  • infection
  • pregnancy
  • transforming growth factor-beta 1
  • trophoblasts

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