Reduction of Influenza Virus Envelope's Fusogenicity by Viral Fusion Inhibitors

ACS Infect Dis. 2016 Jan 8;2(1):47-53. doi: 10.1021/acsinfecdis.5b00109. Epub 2015 Oct 22.

Abstract

During cell entry of an enveloped virus, the viral membrane must be fused with the cellular membrane. The virus envelope has a unique structure consisting of viral proteins and a virus-specific lipid composition, whereas the host membrane has its own structure with host membrane proteins. Compound 136 was previously found to bind in close proximity to the viral envelope and inhibit influenza virus entry. We showed here that the 136-treated influenza virus still caused hemolysis. When liposomes were used as the target membrane for 136-treated viruses, aberrant fusion occurred; few liposomes fused per virion, and glycoproteins were not distributed evenly across fusion complexes. Additionally, large fusion aggregates did not form, and in some instances, neck-like structures were found. Based on previous results and hemolysis, fusion inhibition by 136 occurs post-scission but prior to lipid mixing.

Keywords: fusion inhibitor; fusogenicity; influenza virus; lipid composition; liposome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Hemolysis / drug effects
  • Humans
  • Influenza A virus / drug effects*
  • Influenza A virus / metabolism*
  • Liposomes / metabolism
  • Viral Fusion Protein Inhibitors / pharmacology*
  • Viral Fusion Proteins / antagonists & inhibitors*
  • Viral Fusion Proteins / chemistry
  • Viral Fusion Proteins / metabolism
  • Virus Internalization / drug effects*

Substances

  • Antiviral Agents
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Liposomes
  • Viral Fusion Protein Inhibitors
  • Viral Fusion Proteins