Focused CryoEM Studies of the HIV-1 Capsid Reveal CA Pentamer Structure

The word virus tends to conjure up images of phages, influenza, rhinovirus, and, today, very likely coronaviruses – all with icosahedrally symmetric capsids. Many viruses, however, have irregular and asymmetric capsids. HIV, the pandemic virus that has receded from the public conversation in recent years, has a pleomorphic capsid in the form of an asymmetric, fullerene cone. Both icosahedra and fullerenes are made of hexameric and pentameric building blocks, yet the distribution of pentamers in each capsid dictates the morphology. We show here that the formation of pentamers in the HIV capsid is modulated by a molecular switch in the N-terminal domain of the viral capsid protein, CA. We further show that a ligand binding site located away from the switch affects the equilibrium of the switch conformation, and that ablation of the binding site allows formation of an alternative CA pentamer. These results exemplify the robustness of the capsid lattice and provide new insights on capsid interactions and inhibition.