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Low endocytic pH and capsid protein autocleavage are critical components of Flock House virus cell entry

Amy L Odegard1, Maggie H Kwan, Hanna E Walukiewicz

  • 1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., MB-31, La Jolla, CA 92037, USA.

Journal of Virology
|June 26, 2009
PubMed

Insights

Flock House virus (FHV) uses low pH in endosomes to expose viral peptides that disrupt cell membranes. This mechanism is crucial for viral RNA release into the host cell cytoplasm.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Nonenveloped virus entry into host cells is a critical step in infection but remains incompletely understood.
  • Common mechanisms for viral membrane penetration are emerging, highlighting the need for detailed studies on specific viruses.

Purpose of the Study:

  • To elucidate the mechanism of Flock House virus (FHV) entry and membrane penetration.
  • To investigate the role of endocytic pH and viral particle structural changes in FHV host cell entry.

Main Methods:

  • Correlated in vivo and in vitro studies were employed to analyze FHV entry.
  • Experiments involved assessing FHV infection at different pH levels, liposome disruption assays, and analysis of viral particle properties (hydrophobicity, heat perturbation).
  • Mutant FHV particles defective in autoproteolytic cleavage were used to assess the role of gamma peptide generation.

Main Results:

  • Low endocytic pH is essential for FHV infection and triggers disruption of model membranes (liposomes).
  • Acidic pH exposure increases FHV particle hydrophobicity, and heat treatment enhances liposome disruption, indicating capsid changes.
  • Autoproteolytic cleavage to generate the lipophilic gamma peptide is required for membrane penetration; cleavage-defective mutants failed to lyse liposomes.

Conclusions:

  • FHV enters host cells via endocytosis, with low endocytic pH irreversibly exposing or releasing membrane-active gamma peptides.
  • These exposed gamma peptides disrupt the endosomal membrane, facilitating viral RNA translocation into the cytoplasm.
  • A model for FHV entry is proposed, emphasizing the critical role of pH-triggered gamma peptide release in membrane penetration.

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