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

Area of Science:

• Virology
• Immunology
• Reproductive Biology

Background:

• Zika virus (ZIKV) causes congenital Zika syndrome, but placental infection mechanisms are unclear.
• Transforming growth factor-beta 1 (TGF-β1) is abundant at the maternal-fetal interface during pregnancy.
• TGF-β1 is known to enhance other viral infections in human cells.

Purpose of the Study:

• To investigate the role of TGF-β1 in ZIKV infection of human trophoblast cells.
• To determine if TGF-β1 influences ZIKV binding, entry, and replication in placental cells.

Main Methods:

• Immortalized human first-trimester trophoblasts (Swan.71) were treated with TGF-β1.
• Cells were inoculated with ZIKV (PRVABC59 strain).
• TGF-β/Smad signaling pathway inhibitors (SB431542, SB525334) were used to block TGF-β1 effects.
• Immunofluorescent assay, flow cytometry, and viral replication assays were performed.

Main Results:

• TGF-β1 significantly enhanced ZIKV infection in trophoblast cells.
• TGF-β1 treatment increased ZIKV binding to cells by approximately 2-fold.
• Inhibitors of the TGF-β/Smad pathway abolished the enhanced infection and suppressed viral replication.
• TGF-β1 upregulated the expression of ZIKV receptors Tyro3 and AXL.

Conclusions:

• TGF-β1 promotes ZIKV infection in human trophoblasts, likely via the Smad signaling pathway.
• Increased viral binding and receptor expression contribute to enhanced ZIKV infection.
• These findings suggest a potential mechanism for ZIKV placental barrier crossing.