Rift Valley fever virus infects trophoblast cell lines in an LRP1-dependent manner

Area of Science:

• Virology
• Cell Biology
• Obstetrics

Background:

• Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus causing severe human and livestock disease.
• Vertical transmission of RVFV during pregnancy poses significant risks.
• The mechanism of RVFV entry into human trophoblast cells is not fully understood.

Purpose of the Study:

• To investigate the role of low-density lipoprotein receptor-related protein 1 (LRP1) in RVFV infection of human trophoblast cells.
• To determine if LRP1 is a key factor for RVFV entry into the maternal-fetal interface.

Main Methods:

• Utilized JEG-3, JAR, and HTR-8/SVneo human trophoblast cell lines.
• Assessed RVFV replication and LRP1 expression across cell types.
• Performed competitive inhibition assays using LRP1 ligands (murine RAP domain 3) and LRP1 fragments.

Main Results:

• RVFV replicated to high titers in the studied trophoblast cell lines.
• LRP1 expression levels varied among the different trophoblast cell types.
• RVFV entry into trophoblast cells was significantly inhibited by LRP1-specific ligands, indicating LRP1 dependence.

Conclusions:

• Low-density lipoprotein receptor-related protein 1 (LRP1) is implicated as a critical determinant for RVFV infection of human trophoblast cells.
• LRP1 mediates RVFV entry at the maternal-fetal interface, highlighting a potential target for therapeutic interventions.