Smallpox was a devastating infectious disease that left a lasting mark on human history. Through a concerted global effort, it became the first human disease officially eradicated in 1980. Microscopes played a significant part in this achievement, enabling scientists to understand the virus and aiding diagnostic efforts.
What Smallpox Looks Like Through a Microscope
The Variola virus, responsible for smallpox, belongs to the Poxviridae family and is notably large among viruses. Under an electron microscope, the virus appears as a distinctive brick-like or ovoid particle. Its dimensions are approximately 200 to 400 nanometers by 200 to 270 nanometers, making it one of the biggest viruses known to infect humans. This substantial size allowed for its visualization with early microscopic techniques, though with limited detail.
The virion’s outer surface features ridges arranged in parallel rows, sometimes helically. Inside, a complex internal arrangement includes a biconcave, or dumbbell-shaped, core surrounded by a lipid and protein outer surface. Two “lateral bodies” of unknown function accompany the core, which contains tightly compressed nucleoprotein.
Early light microscopes could not resolve individual virus particles due to their small size. Instead, light microscopy revealed cellular changes within infected tissues, such as characteristic cytoplasmic inclusion bodies. These structures, known as Guarnieri bodies, are sites where the virus replicates and appear as pink masses in stained tissue samples. Electron microscopy provided the resolution necessary to see the actual viral particles, their unique morphology, and internal components, offering a clear visual signature for the Variola virus.
Microscopy’s Pivotal Role in Smallpox Eradication
Microscopes were important throughout the global smallpox eradication campaign, from initial diagnosis to confirming the absence of the virus. Electron microscopy provided a rapid and reliable method for identifying poxvirus particles in patient samples like vesicular fluid or scabs. The distinctive brick-shaped morphology allowed public health workers to quickly confirm an orthopoxvirus infection. This speed was useful in distinguishing poxviruses from other rash-causing illnesses, such as herpesviruses, which have a different, icosahedral shape.
While electron microscopy confirmed an orthopoxvirus infection, it could not definitively differentiate Variola virus from other closely related orthopoxviruses like vaccinia or monkeypox solely based on morphology. However, with clinical presentation and patient history, rapid identification of a poxvirus by electron microscopy aided further laboratory tests, such as PCR assays, for species identification. This multi-pronged diagnostic approach supported surveillance and containment strategies during outbreaks.
Beyond diagnosis, microscopy also contributed to research efforts aimed at understanding the Variola virus. Scientists used microscopes to study the virus’s replication cycle within host cells, observing how it infected cells and assembled new viral particles. This detailed understanding of viral processes was important for developing and improving intervention strategies. The ability to quickly and accurately identify the virus and its effects on cells, in patient samples and laboratory settings, strengthened the global eradication program.