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Chapter 4 : What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy

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Abstract:

This chapter begins with an overview of Rudolf Virchow’s promulgation of cell theory, that the cell must be seen as the fundamental seat of disease pathology. Refinements in techniques of electron microscopy allowed advances in the understanding of viral disease pathogenesis, identification of new viral pathogens, and contributions to the emerging field of rapid viral diagnostics. Virchow enunciated the principles upon which medical research would be based for the next hundred years and more. This accomplishment in cellular pathology proved to be true for diseases caused by viruses, dependent on host cells for replication. The solution of aberrations of the compound microscope and the increased power of resolution brought about the need for improved methods of tissue preparation. Sections cut by hand without fixation or embedded and unstained were of uneven and inconsistent quality and provided little contrast of cellular elements. The chapter talks about the viral inclusion bodies such as Negri Bodies, Guarnieri bodies, elementary bodies, intranuclear inclusions and multinucleated cells. It also deals with viral inclusion body diseases which include rabies, smallpox, varicella and cytomegalic inclusion disease of the newborn. In the coming decades, the rudimentary electron microscopic developments would be complemented by further progress in rapid diagnostic techniques. The application of electron microscopy to the understanding of viruses was revolutionary. It became a very powerful tool for research and diagnostic virology demonstrating the armamentarium of research tools, including light and electron microscopes, experimental animals, and illustrative items.

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4

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Figure 1

Rudolf Virchow caricature. Virchow’s revolutionized pathology, asserting that the cell is the fundamental focus of disease Virchow helped facilitate the modern era of medicine yet was resistant to germ theory. (Courtesy of the National Library of Medicine, Historical Images Collection.) doi:10.1128/9781555818586.ch4.f1

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Image of Figure 2
Figure 2

Advertisement for achromatic microscopes 1859. Optical aberrations, including chromatic aberration, impaired image resolution into the 19th century. This advertisement, from , offers achromatic microscopes for sale in the second half of the 19th century. (Courtesy of the National Library of Medicine, Historical Images Collection.) doi:10.1128/9781555818586.ch4.f2

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 3

Poster of a rabid dog. Perhaps the oldest recognized and most feared transmissible disease, rabies was often incorrectly diagnosed until the description of the Negri body in 1903. (Courtesy of the Historical Library, Yale University School of Medicine.) doi:10.1128/9781555818586.ch4.f3

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 4

Negri bodies in brain. The observation of intracytoplasmic inclusion bodies in the brains of animals was reported by Adelchi Negri in 1903. It became the diagnostic method of choice for decades. Arrows indicate Negri bodies in a brain tissue section. (Courtesy of J. H. Kim, Yale University School of Medicine.) doi:10.1128/9781555818586.ch4.f4

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 5

Varicella-zoster virus inclusions in a monolayer of human diploid fibroblasts. Arrows indicate intranuclear inclusions in a field of multinucleated cells. Hematoxylin and eosin stain. (Collection of Marilyn J. August.) doi:10.1128/9781555818586.ch4.f5

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 6

Tzanck smear. Tzanck smears, performed at the bedside, offer a rapid diagnostic test of various skin lesions. For example, the presence of intranuclear inclusions suggests one of the herpes viruses, as in the example shown. (Collection of Marilyn J. August.) doi:10.1128/9781555818586.ch4.f6

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 7

Cytomegalovirus inclusions. Cytomegalovirus inclusions, originally thought to be parasitic in nature, identified cytomegalic inclusion disease of infants. This image is from the brain of a cytomegalovirus-infected fetus. (Courtesy of J. H. Kim, Yale University School of Medicine.) doi:10.1128/9781555818586.ch4.f7

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 8

Bodo von Borries (left) and Ernst Ruska in the early 1930s on vacation on the island of Ruegen. (Courtesy of the Ernst Ruska Archive, Berlin, Germany.) doi:10.1128/9781555818586.ch4.f8

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 9

Max Knoll (left) and Ernst Ruska with an early transmission electron microscope, the 1933 Uebermikroskop. The photo was taken in the early 1940s. (Courtesy of the Ernst Ruska Archive, Berlin, Germany.) doi:10.1128/9781555818586.ch4.f9

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Figure 10

Helmut Ruska, circa 1930. As the younger brother of Ernst Ruska and trained in medicine, Helmut Ruska pioneered the electron microscopy of viruses. Together with Ernst and his brother-in-law, Bodo von Borries, they published the first electron micrographs of viruses in 1939. This was the first visualization of the particulate nature of viruses. (Courtesy of Ernst Ruska Archive, Berlin, Germany.) doi:10.1128/9781555818586.ch4.f10

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Image of Figure 11
Figure 11

Electron micrograph of poxvirus. Vaccinia and smallpox were early subjects of electron microscopic study, and the brick shape was readily identified. This electron micrograph utilized more advanced techniques than were originally available, such as negative staining, allowing visualization of structural detail. (Courtesy of the CDC, Public Health Image Library.) doi:10.1128/9781555818586.ch4.f11

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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Image of Figure 12
Figure 12

“1887–1987: A Century of Science for Health.” Illustration demonstrating the armamentarium of research tools, including light and electron microscopes, experimental animals, and illustrative items. Each of the tools has been applied to the study and diagnosis of viruses and their infections. (Courtesy of the National Library of Medicine, Historical Images Collection.) doi:10.1128/9781555818586.ch4.f12

Citation: Booss J, August M. 2013. What Can Be Seen: from Viral Inclusion Bodies to Electron Microscopy, p 79-112. In To Catch a Virus. ASM Press, Washington, DC. doi: 10.1128/9781555818586.ch4
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