Influenza demonstrates how rapid changes in a pathogen can arise through the recombination of its genetic material. Influenza, commonly called flu, is a respiratory disease caused by influenza viruses. In the United States, from 5% to 20% of the population is infected with influenza annually, and though most cases are mild, an estimated 36,000 people die from influenza-related causes each year. At certain times, particularly when new strains of influenza virus enter the human population, there are worldwide epidemics (called pandemics); for example, in 1918, the Spanish flu virus killed an estimated 20 million to 100 million people worldwide.

Influenza viruses are RNA viruses that infect birds and mammals. The three main types are influenza A, influenza B, and influenza C. Most cases of the common flu are caused by influenza A and B. Influenza A is divided into subtypes based on the types of two proteins, hemagglutinin (HA) and neuraminidase (NA), found on the surface of the virus. The HA and NA proteins affect the ability of the virus to enter host cells and the host organism’s immune response to infection. There are 16 types of HA and 9 types of NA, which can exist in a virus in different combinations. For example, common strains of influenza circulating in humans today are H1N1 and H3N2 (Table 7.5), along with several strains of influenza B. Most of the different subtypes of influenza A are found in birds.

Although influenza is an RNA virus, it is not a retrovirus: its genome is not copied into DNA and incorporated into the host chromosome like that of a retrovirus. The influenza viral genome consists of seven or eight pieces of RNA that are enclosed in a viral envelope. Each piece of RNA encodes one or two of the virus’s proteins. The virus enters a host cell by attaching to specific receptors on the cell membrane. After the viral particle has entered the cell, the viral RNA is released, copied, and translated into viral proteins. Viral RNA molecules and viral proteins are then assembled into new viral particles, which exit the cell and infect additional cells.

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One of the dangers of the influenza virus is that it evolves rapidly, so that new strains appear frequently. Influenza evolves in two ways. First, each strain continually changes through mutations arising in the viral RNA. The enzyme that copies the RNA is especially prone to making mistakes, so new mutations are continually introduced into the viral genome. This type of continual change is called antigenic drift. Occasionally, major changes in the viral genome take place through antigenic shift, in which genetic material from different strains is combined in a process called reassortment. If a host is simultaneously infected with two different strains, the RNAs of both strains may be replicated within the cell and RNA segments from two different stains may be incorporated into the same viral particle, creating a new strain. For example, in 2002, reassortment between the H1N1 and the H3N2 subtypes created a new H1N2 strain that contained the hemagglutinin from H1N1 and the neuraminidase from H3N2. New strains produced by antigenic shift are responsible for most pandemics because no one has immunity to the radically different virus that is produced.

Birds harbor the most different strains of influenza A, but humans are not easily infected with bird influenza. The appearance of new strains in humans is thought to arise most often from viruses that reassort in pigs, which can be infected by viruses from both humans and birds. In 2009, a new strain of H1N1 influenza (called swine flu) emerged in Mexico and quickly spread throughout the world. This virus arose from a series of reassortment events that combined gene sequences from human, bird, and pig influenza viruses to produce the new H1N1 virus (Figure 7.29). Farming practices that raise pigs and birds in close proximity may facilitate reassortment among avian, swine, and human strains of influenza.