What Does the Smallpox Virus Look Like Under a Microscope?

Smallpox is an infectious disease caused by the Variola virus. Following a successful global vaccination campaign, the disease was officially eradicated in 1980. While no longer a public threat, understanding its physical characteristics provides insight into how it functioned. Examining the virus at a microscopic level reveals a complex and organized structure.

The Variola Virus Structure

The Variola virus particle, or virion, is one of the largest viruses known to infect animals, measuring approximately 300 to 350 nanometers long. This size makes it visible with powerful microscopes, where it displays a distinct brick-like or ovoid shape. Its external surface is not smooth but is covered with ridges that are sometimes arranged in parallel or helical rows.

Internally, the smallpox virion has a complex architecture. At its center is a biconcave or dumbbell-shaped core that houses its genetic material, a single linear double-stranded DNA genome. Flanking the central core are two structures known as lateral bodies, though their exact function remains an area of study.

Poxviruses like Variola are unique among DNA viruses because they replicate within the cytoplasm of the host cell, not the nucleus. To accomplish this, they carry their own specialized proteins, including a DNA-dependent RNA polymerase. During this process, they form characteristic inclusion bodies in the cytoplasm called Guarnieri bodies, which are the sites of viral replication.

Visualizing the Virus

Viruses are far too small to be observed with a standard light microscope. Viewing a particle as minuscule as the Variola virus requires the use of an electron microscope. This instrument uses a beam of electrons instead of light to create a highly magnified image, enabling scientists to see the virus’s detailed structure. Electron microscopy was first used to differentiate between the smallpox and chickenpox viruses based on their appearance.

A Transmission Electron Microscope (TEM) works by passing an electron beam through a very thin slice of a specimen. This method allows for the visualization of the internal structures of the virion, such as the dumbbell-shaped core and lateral bodies. The resulting image is a two-dimensional, black-and-white representation.

For a three-dimensional view of the virus’s exterior, researchers use a Scanning Electron Microscope (SEM). An SEM scans the surface of the specimen with a focused electron beam, which interacts with the surface to create a detailed image of its topography. This technique reveals the brick-like shape and ridged texture of the smallpox virus’s outer surface.

Distinguishing Smallpox from Similar Viruses

On an electron microscope, all orthopoxviruses, the genus to which smallpox belongs, share the same characteristic brick-shaped appearance. This makes it impossible to distinguish Variola virus from vaccinia, cowpox, or monkeypox viruses based on morphology alone. Definitive identification requires advanced laboratory techniques like nucleic acid testing.

A more straightforward visual distinction can be made when comparing smallpox to the chickenpox virus, which is caused by the Varicella-zoster virus. Unlike the large, complex, and ovoid shape of smallpox, the chickenpox virus belongs to the herpesvirus family. Herpesviruses are characteristically icosahedral, meaning they have a 20-sided, roughly spherical shape. This difference in shape provides a clear visual marker to differentiate between the two viruses under an electron microscope.