Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins.
Defensins are peptides that protect the host against microorganisms. Here we show that the theta-defensin retrocyclin 2 (RC2) inhibited influenza virus infection by blocking membrane fusion mediated by the viral hemagglutinin. RC2 was effective even after hemagglutinin attained a fusogenic conformation or had induced membrane hemifusion. RC2, a multivalent lectin, prevented hemagglutinin-mediated fusion by erecting a network of crosslinked and immobilized surface glycoproteins. RC2 also inhibited fusion mediated by Sindbis virus and baculovirus. Human beta-defensin 3 and mannan-binding lectin also blocked viral fusion by creating a protective barricade of immobilized surface proteins. This general mechanism might explain the broad-spectrum antiviral activity of many multivalent lectins of the innate immune system.
Leikina
Eugenia
E
Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-1855, USA.
Delanoe-Ayari
Helene
H
Melikov
Kamran
K
Cho
Myoung-Soon
MS
Chen
Andrew
A
Waring
Alan J
AJ
Wang
Wei
W
Xie
Yongming
Y
Loo
Joseph A
JA
Lehrer
Robert I
RI
Chernomordik
Leonid V
LV
D000890:Anti-Infective Agents / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D045744:Cell Line, Tumor; D023082:Defensins / Q000494:pharmacology*; D004912:Erythrocytes; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008561:Membrane Fusion / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D009975:Orthomyxoviridae / Q000187:drug effects / Q000502:physiology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D014759:Viral Envelope Proteins / Q000187:drug effects / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000187:drug effects / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000890:Anti-Infective Agents; D023082:Defensins; D006389:Hemagglutinins, Viral; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C022012:glycoprotein E1, Sindbis virus; C450142:theta-defensin