Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific viroporin function

Area of Science:

• Virology
• Membrane protein function
• Antiviral drug development

Background:

• Viroporins are viral proteins crucial for virus assembly and release.
• Blocking viroporin activity is a promising antiviral strategy.
• Classical swine fever virus (CSFV) protein p7 is identified as a class II viroporin.

Purpose of the Study:

• To identify the specific regions of CSFV protein p7 responsible for its membrane permeabilization activity.
• To develop a minimal model system for studying CSFV p7 function.
• To understand the structural determinants of viroporin activity.

Main Methods:

• Utilized an overlapping peptide library to map functional domains.
• Assessed protein activity in a minimal model membrane system.
• Investigated the influence of pH, channel blockers, and lipid composition.

Main Results:

• The C-terminal hydrophobic stretch (residues 39-67) was identified as the primary porating domain.
• A preceding polar sequence (residues 33-38) is necessary for pH dependence and channel blocker sensitivity.
• A peptide encompassing residues 33-67 serves as a valid surrogate for studying p7 activity in model membranes.

Conclusions:

• CSFV protein p7's viroporin function is mediated by a specific peptide sequence (residues 33-67).
• This minimal peptide can be used to study CSFV p7 activity in model systems.
• CSFV p7 likely employs genus-specific mechanisms for its function, offering potential antiviral targets.