Focus on the Flu Research: Flu Primer

A flu virus is roughly round, but it can also be elongated or irregularly shaped. Inside are eight segments of single-strand RNA containing the genetic instructions for making new copies of the virus. Flu's most striking feature is a layer of spikes projecting from its surface. There are two different types of spikes: one is the protein hemagglutinin (HA), which allows the virus to "stick" to a cell and initiate infection, the other is a protein called neuraminidase (NA), which enables newly formed viruses to exit the host cell.

Influenza viruses are classified as type A, B, or C based upon their protein composition. Type A viruses are found in many kinds of animals, including ducks, chickens, pigs, whales, and also in humans. The type B virus widely circulates in humans. Type C has been found in humans, pigs, and dogs and causes mild respiratory infections, but does not spark epidemics.

Type A influenza is the most frightening of the three. It is believed responsible for the global outbreaks of 1918, 1957 and 1968. Type A viruses are subdivided into groups based on two surface proteins, HA and NA. Scientists have characterized 16 HA subtypes and 9 NA subtypes.

Type A subtypes are classified by a naming system that includes the place the strain was first found, a lab identification number, the year of discovery, and, in parentheses, the type of HA and NA it possesses, for example, A/Hong Kong/156/97 (H5N1). If the virus infects non-humans, the host species is included before the geographical site, as in A/Chicken/Hong Kong/G9/97 (H9N2). There are no type B or C subtypes.

In nature, the flu virus is found in wild aquatic birds such as ducks and shore birds. It has persisted in these birds for millions of years and does not typically harm them. But the frequently mutating flu viruses can readily jump the species barrier from wild birds to domesticated ducks and then to chickens. From there, the next stop in the infectious chain is often pigs.

Pigs can be infected by both bird (avian) influenza and the form of influenza that infects humans. In a setting such as a farm where chickens, humans and pigs live in close proximity, pigs act as an influenza virus mixing bowl. If a pig is infected with avian and human flu simultaneously, the two types of virus may exchange genes. Such a "reassorted" flu virus can sometimes spread from pigs to people.

Depending on the precise assortment of bird-type flu proteins that make it into the human population, the flu may be more or less severe.

In 1997, for the first time, scientists found that bird influenza skipped the pig step and infected humans directly. Alarmed health officials feared a worldwide epidemic (a pandemic). But, fortunately, the virus could not pass between people and thus did not spark an epidemic. Scientists speculate that chickens may now also have the receptor used by human-type viruses.

Influenza virus is one of the most changeable of viruses. These genetic changes may be small and continuous or large and abrupt.

Small, continuous changes happen in type A and type B influenza as the virus makes copies of itself. The process is called antigenic drift. The drifting is frequent enough to make the new strain of virus often unrecognizable to the human immune system. For this reason, a new flu vaccine must be produced each year to combat that year's prevalent strains.

Type A influenza also undergoes infrequent and sudden changes, called antigenic shift. Antigenic shift occurs when two different flu strains infect the same cell and exchange genetic material. The novel assortment of HA or NA proteins in a shifted virus creates a new influenza A subtype. Because people have little or no immunity to such a new subtype, their appearance tends to coincide with very severe flu epidemics or pandemics.

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