Chapter III. General Influenza Viruses

Overview

There are three types of influenza viruses: A, B, and C. Only influenza A viruses are further classified by subtype on the basis of the two main surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Influenza A subtypes and B viruses are further classified by strains.

How Influenza Viruses Change: Drift and Shift

Influenza viruses are dynamic and are continuously evolving. Influenza viruses can change in two different ways: antigenic drift and antigenic shift. Influenza viruses are changing by antigenic drift all the time, but antigenic shift happens only occasionally. Influenza type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift.

Antigenic drift refers to small, gradual changes that occur through point mutations in the two genes that contain the genetic material to produce the main surface proteins, hemagglutinin, and neuraminidase. These point mutations occur unpredictably and result in minor changes to these surface proteins. Antigenic drift produces new virus strains that may not be recognized by antibodies to earlier influenza strains. This process works as follows: a person infected with a particular influenza virus strain develops antibody against that strain. As newer virus strains appear, the antibodies against the older strains might not recognize the "newer" virus, and infection with a new strain can occur. This is one of the main reasons why people can become infected with influenza viruses more than one time and why global surveillance is critical in order to monitor the evolution of human influenza virus stains for selection of which strains should be included in the annual production of influenza vaccine. In most years, one or two of the three virus strains in the influenza vaccine are updated to keep up with the changes in the circulating influenza viruses. For this reason, people who want to be immunized against influenza need to be vaccinated every year.

Antigenic shift refers to an abrupt, major change to produce a novel influenza A virus subtype in humans that was not currently circulating among people (see more information below under Influenza Type A and Its Subtypes). Antigenic shift can occur either through direct animal (poultry)-to-human transmission or through mixing of human influenza A and animal influenza A virus genes to create a new human influenza A subtype virus through a process called genetic reassortment. Antigenic shift results in a new human influenza A subtype. A global influenza pandemic (worldwide spread) may occur if three conditions are met:

• A new subtype of influenza A virus is introduced into the human population.
• The virus causes serious illness in humans.
• The virus can spread easily from person to person in a sustained manner.

Types, Subtypes, and Strains

Influenza Type A and Its Subtypes

Influenza type A viruses can infect people, birds, pigs, horses, and other animals, but wild birds are the natural hosts for these viruses. Influenza type A viruses are divided into subtypes and named on the basis of two proteins on the surface of the virus: hemagglutinin (HA) and neuraminidase (NA). For example, an "H7N2 virus" designates an influenza A subtype that has an HA 7 protein and an NA 2 protein. Similarly an "H5N1" virus has an HA 5 protein and an NA 1 protein. There are 16 known HA subtypes and 9 known NA subtypes. Many different combinations of HA and NA proteins are possible. Only some influenza A subtypes (i.e., H1N1, H1N2, and H3N2) are currently in general circulation among people. Other subtypes are found most commonly in other animal species. For example, H7N7 and H3N8 viruses cause illness in horses, and H3N8 also has recently been shown to cause illness in dogs.

Only influenza A viruses infect birds, and all known subtypes of influenza A viruses can infect birds. However, there are substantial genetic differences between the influenza A subtypes that typically infect birds and those that infect both people and birds. Three prominent subtypes of the avian influenza A viruses that are known to infect both birds and people are:

Influenza A H5

Nine potential subtypes of H5 are known. H5 infections, such as HPAI H5N1 viruses currently circulating in Asia and Europe, have been documented among humans and sometimes cause severe illness or death.

Influenza A H7

Nine potential subtypes of H7 are known. H7 infection in humans is rare but can occur among persons who have direct contact with infected birds. Symptoms may include conjunctivitis and/or upper respiratory symptoms. H7 viruses have been associated with both LPAI (e.g., H7N2, H7N7) and HPAI (e.g., H7N3, H7N7), and have caused mild to severe and fatal illness in humans.

Influenza A H9

Nine potential subtypes of H9 are known; influenza A H9 has rarely been reported to infect humans. However, this subtype has been documented only in a low pathogenic form.

Influenza Type B

Influenza B viruses are usually found only in humans. Unlike influenza A viruses, these viruses are not classified according to subtype. Influenza B viruses can cause morbidity and mortality among humans, but in general are associated with less severe epidemics than influenza A viruses. Although influenza type B viruses can cause human epidemics, they have not caused pandemics.

Influenza Type C

Influenza type C viruses cause mild illness in humans and do not cause epidemics or pandemics. These viruses are not classified according to subtype.

Strains

Influenza B viruses and subtypes of influenza A virus are further characterized into strains. There are many different strains of influenza B viruses and of influenza A subtypes. New strains of influenza viruses appear and replace older strains. This process occurs through antigenic drift. When a new strain of human influenza virus emerges, antibody protection that may have developed after infection or vaccination with an older strain may not provide protection against the new strain. Therefore, the influenza vaccine is updated on a yearly basis to keep up with the changes in influenza viruses.

Avian Influenza A Viruses

Influenza viruses that infect birds are called avian influenza viruses. Only influenza A viruses infect birds, and all known subtypes of influenza A viruses can infect birds. However, there are substantial genetic differences between the subtypes that typically infect both people and birds. Within subtypes of avian influenza A viruses there also are different strains (described in Influenza Viruses - Types, Subtypes, and Strains).

Avian influenza A H5 and H7 viruses can be distinguished as "low pathogenic" and "high pathogenic" forms on the basis of genetic features of the virus and the severity of the illness they cause in poultry; influenza H9 virus has been identified only in a "low pathogenicity" form. Each of these three avian influenza A viruses (H5, H7, and H9) theoretically can be partnered with any one of nine neuraminidase surface proteins; thus, there are potentially nine different forms of each subtype (e.g., H5N1, H5N2, H5N3, H5N9).

Summary information follows about these three prominent subtypes of avian influenza A viruses:

Influenza A H5

• Potentially nine different subtypes
• Can be highly pathogenic or low pathogenic
• H5 infections have been documented among humans, sometimes causing severe illness and death

Influenza A H7

• Potentially nine different subtypes
• Can be highly pathogenic or low pathogenic
• H7 infection in humans is rare, but can occur among persons who have direct contact with infected birds; symptoms may include conjunctivitis and/or upper respiratory symptoms

Influenza A H9

• Potentially nine different subtypes
• Documented only in low pathogenic form

At least three H9 infections in humans have been confirmed