Reduction of Influenza Virus Envelope's Fusogenicity by Viral Fusion Inhibitors.
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.
Department of Microbiology, University of Alabama at Birmingham , 1025 18th Street South, Birmingham, Alabama 35294, United States.
Michael
M
Rowse
Department of Microbiology, University of Alabama at Birmingham , 1025 18th Street South, Birmingham, Alabama 35294, United States.
Shihong
S
Qiu
Department of Microbiology, University of Alabama at Birmingham , 1025 18th Street South, Birmingham, Alabama 35294, United States.
Jun
J
Tsao
Institute of Biochemistry, ETH Zurich , HPM E8.2, Otto-Stern-Weg 3, 8093 Zurich, Switzerland.
Yohei
Y
Yamauchi
Laboratory of Structural Biology, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen 518055, China.
Guoxin
G
Wang
Laboratory of Structural Biology, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen 518055, China.|Department of Chemistry College of Arts and Sciences, Georgia State University , Atlanta, Georgia 30302, United States.
Ming
M
Luo
D000998:Antiviral Agents / Q000494:pharmacology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D065147:Viral Fusion Protein Inhibitors / Q000494:pharmacology*; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008081:Liposomes; D065147:Viral Fusion Protein Inhibitors; D014760:Viral Fusion Proteins
fusion inhibitor; fusogenicity; influenza virus; lipid composition; liposome