tetano
Editor, Senior Moderator
J Biol Chem. 2011 Oct 12. [Epub ahead of print]
Capturing a fusion intermediate of influenza hemagglutinin with a cholesterol-conjugated peptide: a new antiviral strategy for influenza virus.
Lee KK, Pessi A, Gui L, Santoprete A, Talekar A, Moscona A, Porotto M.
Source
University of Washington, United States;
Abstract
We previously described fusion-inhibitory peptides that are targeted to the cell membrane by cholesterol-conjugation, and potently inhibit enveloped viruses that fuse at the cell surface, including HIV, parainfluenza, and henipaviruses. However, for viruses that fuse inside intracellular compartments, fusion-inhibitory peptides have exhibited very low antiviral activity. We propose that for these viruses too, membrane targeting via cholesterol conjugation may yield potent compounds. Here we compare the activity of fusion-inhibitory peptides derived from the influenza hemagglutinin (HA), and show that the while the unconjugated peptides are inactive, the cholesterol conjugated compounds are effective inhibitors of infectivity and membrane fusion. We hypothesize that the cholesterol moiety , by localizing the peptides to the target cell membrane, allows the peptides to follow the virus to the intracellular site of fusion. The cholesterol conjugated peptides trap HA in a transient intermediate state, after fusion is triggered but before completion of the refolding steps that drive merger of the viral and cellular membranes. These results provide proof of concept for an antiviral strategy that is applicable to intracellularly-fusing viruses, including known and emerging viral pathogens.
PMID:
21994935
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21994935
Capturing a fusion intermediate of influenza hemagglutinin with a cholesterol-conjugated peptide: a new antiviral strategy for influenza virus.
Lee KK, Pessi A, Gui L, Santoprete A, Talekar A, Moscona A, Porotto M.
Source
University of Washington, United States;
Abstract
We previously described fusion-inhibitory peptides that are targeted to the cell membrane by cholesterol-conjugation, and potently inhibit enveloped viruses that fuse at the cell surface, including HIV, parainfluenza, and henipaviruses. However, for viruses that fuse inside intracellular compartments, fusion-inhibitory peptides have exhibited very low antiviral activity. We propose that for these viruses too, membrane targeting via cholesterol conjugation may yield potent compounds. Here we compare the activity of fusion-inhibitory peptides derived from the influenza hemagglutinin (HA), and show that the while the unconjugated peptides are inactive, the cholesterol conjugated compounds are effective inhibitors of infectivity and membrane fusion. We hypothesize that the cholesterol moiety , by localizing the peptides to the target cell membrane, allows the peptides to follow the virus to the intracellular site of fusion. The cholesterol conjugated peptides trap HA in a transient intermediate state, after fusion is triggered but before completion of the refolding steps that drive merger of the viral and cellular membranes. These results provide proof of concept for an antiviral strategy that is applicable to intracellularly-fusing viruses, including known and emerging viral pathogens.
PMID:
21994935
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21994935