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The ability of viruses to cause disease can be viewed on two distinct levels: (1) the changes that occur within individual cells and (2) the process that takes place in the infected patient.
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There are four main effects of virus infection on the cell: (1) death, (2) fusion of cells to form multinucleated cells, (3) malignant transformation, and (4) no apparent morphologic or functional change.
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Death of the cell is probably due to inhibition of macromolecular synthesis. Inhibition of host cell protein synthesis frequently occurs first and is probably the most important effect. It is important to note that synthesis of cellular proteins is inhibited but viral protein synthesis still occurs. For example, poliovirus inactivates an initiation factor (IF) required for cellular mRNA to be translated into cellular proteins, but poliovirus mRNA has a special ribosome-initiating site that allows it to bypass the IF so that viral proteins can be synthesized.
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Apoptosis is also involved in cell death caused by viruses. Apoptosis is mediated by caspases, a family of cysteine proteases. The activation of caspases by cytochrome C released from mitochondria damaged by viral infection is an important mechanism.
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Infected cells frequently contain inclusion bodies, which are discrete areas containing viral proteins or viral particles. They have a characteristic intranuclear or intracytoplasmic location and appearance depending on the virus. One of the best examples of inclusion bodies that can assist in clinical diagnosis is that of Negri bodies, which are eosinophilic cytoplasmic inclusions found in rabies virus-infected brain neurons. Another important example is the owl’s eye inclusion seen in the nucleus of cytomegalovirus (CMV)-infected cells. Electron micrographs of inclusion bodies can also aid in the diagnosis when virus particles of typical morphology are visualized.
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Fusion of virus-infected cells produces multinucleated giant cells, which characteristically form after infection with herpesviruses and paramyxoviruses. Fusion occurs as a result of cell membrane changes, which are probably caused by the insertion of viral proteins into the membrane. The clinical diagnosis of herpesvirus skin infections is aided by the finding of multinucleated giant cells with intranuclear inclusions in skin scrapings.
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A hallmark of viral infection of the cell is the cytopathic effect (CPE). This change in the appearance of the infected cell usually begins with a rounding and darkening of the cell and culminates in either lysis (disintegration) or giant cell formation. In the clinical laboratory, detection of virus in a patient’s specimen is frequently based on the appearance of CPE in cell culture. In addition, CPE is the basis for the plaque assay, an important method for quantifying the amount of virus in a sample.
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Infection with certain viruses causes malignant transformation, which is characterized by unrestrained growth, prolonged survival, and morphologic changes such as focal areas of rounded, piled-up cells. These ...