Contrasting effects of filamin A and B proteins in modulating filovirus entry

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Ebola virus (EBOV) and Marburg virus (MARV) are filoviruses causing severe hemorrhagic fevers with high mortality.
• Understanding filovirus-host interactions is crucial for developing effective therapeutics.
• Filovirus entry into host cells is primarily mediated by actin-dependent macropinocytosis, involving viral glycoproteins (eGP and mGP).

Purpose of the Study:

• To identify host cell factors regulating EBOV and MARV entry.
• To investigate the role of actin-binding proteins, specifically filamin A (FLNa) and filamin B (FLNb), in filovirus lifecycle.
• To elucidate the mechanisms by which FLNa and FLNb influence viral entry.

Main Methods:

• Utilized knockdown cell models (FLNaKD and FLNbKD) to assess viral entry.
• Tested entry of pseudotyped viruses (psVSV-RFP-eGP) and infectious recombinant viruses (rVSV-eGP-mCherry).
• Assessed entry of authentic EBOV and MARV in filamin-depleted cells.

Main Results:

• Filamin A knockdown (FLNaKD) significantly inhibited the entry of EBOV and MARV.
• Filamin B knockdown (FLNbKD) surprisingly enhanced the entry of both EBOV and MARV.
• Differential regulation of macropinocytosis by FLNa and FLNb appears to underlie their distinct effects on viral entry.

Conclusions:

• Filamin A and B are identified as novel regulators of EBOV and MARV entry.
• FLNa and FLNb play opposing roles in mediating filovirus cell entry.
• These findings offer potential new strategies for developing countermeasures against EBOV and MARV infections.