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The term influenza represents both a clinically defined respiratory illness accompanied by systemic symptoms of fever, malaise, and myalgia and the name of the orthomyxoviruses that cause this syndrome. Although this term is sometimes used more generally to denote any viral respiratory illness, many features distinguish influenza from these other illnesses, most particularly its systemic symptoms, its propensity to cause sharply peaked winter epidemics, and its capacity to spread rapidly among close contacts. The morbidity and mortality associated with influenza epidemics are documented closely in the United States by the Centers for Disease Control and Prevention (CDC), which records clinical cases of influenza-like illness, cases of virologically documented influenza, and excess deaths due to pneumonia and influenza combined.


Three influenza viruses occur in humans: A, B, and C. These viruses are irregularly circular in shape, measure 80–120 nm in diameter, and have a lipid envelope and prominent spikes that are formed by the two surface glycoproteins, hemagglutinin (H) and neuraminidase (N) (Fig. 195-1). The hemagglutinin functions as the viral attachment protein, binding to sialic acid receptors on the cells that line the superficial epithelium of the respiratory tract. The neuraminidase cleaves the virus from the cell membrane to facilitate its release from the cell and prevents self-aggregation of viruses. Influenza A viruses have eight single-strand negative-sense RNA segments in their genomes that encode hemagglutinin and neuraminidase as well as internal genes, including polymerase, matrix, nucleoprotein, and nonstructural genes. The segmented nature of the genome allows gene reassortment; an analogy for reassortment is the shuffling of a deck of cards. Reassortment takes place when a single cell is infected with two different strains.

FIGURE 195-1

An electron micrograph of influenza A virus (x40,000). (Reprinted with permission from YZ Cohen, R Dolin: Influenza, in Harrison’s Principles of Internal Medicine, 19th ed. DL Kasper et al [eds]. New York: McGraw-Hill, 2015, p 1209.)

Among the influenza viruses, the A viruses are of paramount importance for several reasons: (1) the plasticity of their genomes, which enables them to react to the prevailing immunity in the community by modifying their immunogenic epitopes, particularly on the hemagglutinin surface protein (antigenic drift); (2) the segmentation of their genomes, which allows genes coding both surface and internal proteins to be reassorted between influenza A variants (antigenic shift); and (3) their extensive mammalian and avian reservoirs, in which multiple variants with distinct hemagglutinin and neuraminidase genes lie in wait. As a result of all of these factors, influenza A virus has the ability, particularly after an antigenic shift, to cause a worldwide epidemic (pandemic). The most severe influenza A pandemic in modern history took place in 1918; ~50 million deaths were attributed to the culpable influenza A H1N1 virus in the years surrounding 1918.


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