RNase L interacts with Filamin A to regulate actin dynamics and barrier function for viral entry

Area of Science:

• Cellular biology
• Virology
• Immunology

Background:

• The actin cytoskeleton forms a physical barrier against viral entry.
• Host cells sense pathogen presence to activate innate immunity.
• Mechanisms linking physical pathogen signals to immune responses are not fully understood.

Purpose of the Study:

• To investigate the novel interaction between RNase L and Filamin A in preventing viral entry.
• To elucidate the dual roles of RNase L in host defense.
• To understand how virus infection disrupts this interaction to initiate antiviral signaling.

Main Methods:

• Genetic deletion of RNase L and Filamin A in cells.
• Analysis of viral entry in cells lacking these proteins.
• Use of RNase L deletion mutants to assess Filamin A interaction.
• Transfection of wild-type and mutant RNase L into deficient cells.

Main Results:

• Cells lacking RNase L or Filamin A showed increased viral entry.
• Absence of both proteins exacerbated viral entry.
• RNase L-Filamin A complex disruption is crucial for RNase L's enzymatic antiviral activity.
• RNase L restricts viral entry independently of its enzymatic activity.

Conclusions:

• RNase L and Filamin A form a complex that acts as a physical barrier to viral entry.
• This interaction is independent of RNase L's enzymatic function.
• Virus infection disrupts the complex, releasing RNase L for its canonical antiviral functions.
• RNase L possesses dual roles in innate immunity: a constitutive barrier and an inducible antiviral effector.