Enhanced Detection of Influenza Virus by Viral Membrane Fusion with Membrane Rigidity Modulation of Sialic Acid-Expressing Liposomes

Specific interactions between viruses and host cells provide essential insights into materials science-based strategies to deal with emerging viral diseases. In several viral families, pH-triggered viral fusion is universal and important for understanding the viral infection cycle. Inspired by this process, virus detection has been achieved using nanomaterials with host-mimetic membranes that allow interaction with amphiphilic viral haemagglutinin fusion peptides. Most research has focused on the design of functional nanoparticles with fusogenic capability for virus detection, and there has been little exploitation of membrane rigidity to alter the ability of nanoparticles to interact with the viral membrane and improve their sensing performance. In this study, a homogeneous fluorescent assay using sialic acid-expressing liposomes with tunable responsiveness to external stimuli is developed for the rapid and straightforward detection of an activated influenza A virus. Membrane fusion between the liposome and virus can be easily controlled by varying the membrane rigidity, which is determined by the cholesterol ratio, resulting in fluorescent signals within 30 min and detection of several influenza viruses, including H9N2, CA04(H1N1) and H4N6. Therefore, the designs demonstrated in this study propose underlying approaches to utilize engineered liposomes by modulating their membrane rigidity for the direct and sensitive identification of infectious viruses.