National Institute of Allergy and Infectious Diseases, NIH Volume 2;
I N F E C T I O U S D I S E A S E® Vassil St. Georgiev, Series Editor National Institute of Allergy and Infectious Diseases, NIH Volume 2: Impact on Global Health Vassil St. Georgiev, PhD with Foreword by Antony S. Fauci, MD National Institute of Allergy
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Influenza
Influenza is a highly contagious, acute respiratory illness afflicting humans. Although influenza epidemics occur frequently, their severity varies (1). Not until 1933, when the first human influenza virus was isolated, was it possible to define with certainty which pandemics were caused by influenza viruses. In general, influenza A viruses are more pathogenic than are influenza B viruses. Influenza A virus is a zoonotic infection, and more than 100 types of influenza A viruses infect most species of birds, pigs, horses, dogs, and seals. It is believed that the 1918–1919 pandemic originated from a virulent strain of H1N1 from pigs and birds. The natural reservoir of influenza viruses was identified as wild aquatic birds, from whose populations viruses with new surface proteins could emerge through reassortment. However, it is still not possible to predict how and when new influenza strains will emerge or how virulent a new strain will prove (2). Currently, influenza A viruses of subtypes H1N1 and H3N2 and influenza B viruses of two antigenically distinct hemagglutinin lineages are present in human populations. The occurrence of sporadic avian influenza subtypes (e.g., H9, H7, and particularly H5) in human populations have led to widespread concerns about the possibility of an influenza pandemic. Since 1889, at least five major pandemics have been recorded, when new hemagglutinin and/or neuraminidase subtypes have been introduced into human populations. The pandemic of 1918–1919 was by far the worst of its kind. It was followed by pandemics of decreasing severity in 1957 (Asian flu; subtype H2N2), 1968 (Hong Kong flu; subtype H3N2), and 1977 (Russian flu; subtype H1N1).
13.1 Pathophysiology Based on the antigenic differences between their nucleoprotein (NP) and matrix (M) protein antigens, the influenza viruses are divided into types A, B, and C (1). The influenza A viruses are further divided into subtypes.
The influenza viruses are single-stranded RNA viruses and share structural and biological similarities. The viral RNA core consists of 8 gene segments surrounded by a coat of 10 (influenza A) or 11 (influenza B) proteins. Immunologically, the most important surface proteins are hemagglutinin and neuraminidase, as the influenza viruses are typed on the basis of these proteins. For example, influenza A subtype H3N2 expresses hemagglutinin 3 and neuraminidase 2. The most prevalent human influenza A strains are H1N1 and H3N2. Although the morphologic characteristics of the influenza viruses are a genetic trait, the spherical morphology appears to be dominant on passage in chicken embryos or tissue culture systems. The most distinct feature of the influenza virions is the presence of a layer of spikes projecting radially outward over the surface. The surface spikes are of two distinct types, corresponding with the hemagglutinin and neuraminidase components of the virus.
13.1.1 Hemagglutinin The hemagglutinin (HA) is the surface glycoprotein, which accounts for approximately 25% of viral protein and is d
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