Measuring Adhesion Forces Between Influenza Virus and Living Cells

Abstract

Influenza virus belongs to a wide range of viruses that are enclosed in a lipid envelope. The major spike protein of the viral envelope hemagglutinin (HA) binds sialic acid (SA) residues of glycoproteins on the plasma membrane of the host cells. This represents the first step of infection and requires multiple simultaneous interactions since the affinity between one single HA-SA pair is estimated to be very low (10-13 M-1). The attachment of influenza virus particles to living host cells was characterised on the level of single molecules using optical tweezers and atomic force spectroscopy. Unbinding events where analysed and revealed a multimodal rupture force distribution. This suggests sequential binding of multiple receptors. Treatment of the cells with neuraminidase (NA) which cleaves terminal sialic acid residues leads to a decrease of the binding probability by >50 %. This indicates a specific interaction between hemagglutinin and sialic acid unravelled by force measurements.