Correlative light and electron microscopy methods for the study of virus-cell interactions

Electron microscopy (EM) is an invaluable tool to study the interactions of viruses with cells, and the ultrastructural changes induced in host cells by virus infection. Light microscopy (LM) is a complementary tool with the potential to locate rare events, label specific components, and obtain dynamic information. The combination of LM and EM in correlative light and electron microscopy (CLEM) is particularly powerful. It can be used to complement a static EM image with dynamic data from live imaging, identify the ultrastructure observed in LM, or, conversely, provide molecular specificity data for a known ultrastructure. Here, we describe methods and strategies for CLEM, discuss their advantages and limitations, and review applications of CLEM to study virus-host interactions.