Catching HIV ‘in the act’ with 3D electron microscopy

• Native HIV Env structure can be determined by cryo-electron tomography.
• Focused ion beam scanning electron microscopy (FIB-SEM) reveals the 3D ultrastructure of HIV virological synapses.
• Cryo-electron microscopy of HIV protein complexes can provide key information for vaccine design.

The development of a safe, effective vaccine to prevent HIV infection is a key step for controlling the disease on a global scale. However, many aspects of HIV biology make vaccine design problematic, including the sequence diversity and structural variability of the surface envelope glycoproteins and the poor accessibility of neutralization-sensitive epitopes on the virus. In this review, we discuss recent progress in understanding HIV in a structural context using emerging tools in 3D electron microscopy, and outline how some of these advances could be important for a better understanding of mechanisms of viral entry and for vaccine design.