Recent progresses in thecharacterization of physical properties of viruses allow for the first time toinvestigate distinct virus cycle events at the single particle level. Thesemethodologies have been applied to viruses such as bacteriophages, to which thelinkage between capsid physical properties and function is clear. Such alinkage is not obvious in a retrovirus such as HIV-1. Using a combination ofexperimental approaches based on atomic force microscopy, protein design andbiochemistry, we study the mechanism that governs the entry of HIV-1 intotarget cells. We find that the structural reorganization during viralmaturation is accompanied by a dramatic change in the particle physicalproperties. The mature state of the virus is 14 fold softer than the immaturestate. We further show that this viral “mechanical switch” is required forviral entry, thus revealing a linkage between HIV-1 physical properties andentry activity.
