Do viruses subvert cholesterol homeostasis to induce host cubic membranes?

Biological membranes with cubic morphology are a hallmark of stressed or diseased cellular conditions; both protein–protein interactions and lipid alterations appear to contribute to their biogenesis, yet their specific cellular functions are unknown. The occurrence of cubic membranes strikingly correlates with viral infections; notably, virus entry, proliferation, and release are processes closely linked to cellular cholesterol metabolism, and dys-regulation of cholesterol synthesis at the level of HMG-CoA reductase also induces cubic membrane formation, in the absence of viral infection. We propose that virus-induced cubic membranes could result from viral interference of cellular cholesterol homeostasis, generating a protective membrane environment to facilitate virus assembly and proliferation. Preventing cubic membrane formation might thus disrupt the ‘virus factory’ and offer new avenues to combat viral infections.