Unraveling the architecture of viruses by high-resolution atomic force microscopy

Atomic force microscopy (AFM) has recently emerged as an effective complement to other structure determination techniques for studying virus structure and function. AFM allows the direct visualization of viruses in a hydrated state and can probe surface topography in unrivaled detail. Moreover, AFM can be used to elucidate dynamic processes associated with the life cycle of viruses in vitro. It can readily produce high-resolution, nonaveraged, single-particle images of both polymorphic and pleiomorphic viruses. Although AFM does not yield images of internal structures within an intact virion as do penetrating techniques such as electron microscopy and X-ray crystallography, nonetheless, by visualizing the surfaces of internal structures upon treatment with chemical and enzymatic agents, as we demonstrated recently with vaccinia virus, modeling of the complex architecture of a large virus is possible.