Location: Foreign Animal Disease Research
Title: Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific viroporin function Authors
|Largo, Eneko -|
|Gladue, Douglas -|
|Huarte, Nera -|
|Nieva, Jose -|
Submitted to: Antiviral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 22, 2013
Publication Date: November 2, 2013
Citation: Largo, E., Gladue, D.P., Huarte, N., Borca, M.V., Nieva, J.L. 2013. Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific viroporin function. Antiviral Research. 101:30-36. Interpretive Summary: Classical Swine Fever Virus (CSFV) is a highly contagious and economically significant viral disease effecting pigs. Our research program is aimed at developing coutermeasures against CSFV to minimize the economic impact of potential outbreaks. As part of this research we are studying the role of viral proteins in causing infection and disease. We previously characterized a viral protein called p7 and showed it is a viroporin, that is responsible for formation of pores in the membrane of the infected cells facilitating the egress of the virus. Here we have localized the area of p7 that actually mediates pore formation using a set of synthetic peptides. We also showed that blocking the viroporin function inhibited viral egress and the spread of the virus to surrounding cells. This viroporin thus constitutes a target in antiviral development that could be used in coutermeasure development against this devastating disease of swine.
Technical Abstract: Viroporins are small integral membrane proteins functional in viral assembly and egress by promoting permeabilization. Blocking of viroporin function therefore constitutes a target for antiviral development. Classical swine fever virus (CSFV) protein p7 has been recently regarded as a class II viroporin. Here, we sought to establish the determinants of the CSFV p7 permeabilizing activity in a minimal model system. Assessment of an overlapping peptide library mapped the porating domain to the C-terminal hydrophobic stretch (residues 39-67). Pore-opening dependence on pH or sensitivity to channel blockers observed for the full protein required the inclusion of a preceding polar sequence (residues 33-38). Effects of lipid composition and structural data further support that the resulting peptide (residues 33-67), may comprise a bona fide surrogate to assay p7 activity in model membranes. Our observations imply that CSFV p7 relies on genus-specific structures-mechanisms to perform its viroporin function.