Figure 2.

A possible mechanism of IFITMs inhibition during infection. After receptor/co-receptor binding, several Env trimers cluster for efficient membrane fusion to occur, similarly to cellular receptors on cellular membranes. This clustering event consists in the lateral displacement of several Env proteins through the lipid bilayer. By rigidifying their environment, IFITMs may interfere with the movements of Env molecules impeding clustering and therefore fusion. We hypothesize that a possible manner to circumvent this block is through Env proteins that display higher affinities for their receptor and that therefore require the lateral displacement of fewer Env trimers in order to start membrane fusion. Alternatively, through their action on viral membranes, IFITMs may perturb the overall structural conformation of the gp120-gp41-MA axis, an effect that would more drastically alter less stable gp120 trimers. For simplicity, the possible effects of IFITMs on clustering are depicted only in the case of the negative imprinting of virion particles infectivity, although the model can apply also to target cell protection. Alternative models of IFITMs inhibition are not presented in the figure.