Focus on the Flu

by National Institute of Health

What We Know About the Flu Virus

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.

Virus A, B, C

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.

Naming Viral Strains

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.

Where Influenza Comes From

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.

Drifting and Shifting

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.

Immune Response to the Flu

Landmark Immunity Study Could Give Vaccine Research a Shot in the Arm

By its very nature, influenza poses a serious threat to become a pandemic. For this reason, scientists are also concerned that a genetically altered version of the flu virus might be used in a bioterror attack.

To better understand the issue, researchers at Stanford University's NIAID-funded Cooperative Center for Translational Research on Human Immunology and Biodefense are analyzing the body's immune response to the influenza virus. By focusing on how the body wages war against the flu, the researchers hope to identify new vaccine strategies to better protect against a pandemic strain.

In this study, center director Ann Arvin, M.D., and co-director Harry Greenberg, M.D., are comparing the body's responses to two widely used influenza vaccines: the inactivated flu vaccine, which delivers killed virus through a shot in the arm, and the live attenuated influenza vaccine, which delivers live, weakened virus through a nasal spray.

"Our goal is to conduct a side-by-side comparison of the immune responses induced by these two very different vaccines, both of which work well but in different ways," says Dr. Arvin.

The researchers will examine how the two vaccines influence T-cell and B-cell immune responses, including the production of antibodies, in children as well as in adults. In addition, the research team will observe the activity of natural killer cells, cells that nonspecifically destroy virus-infected cells, to determine if they play a role in the body's early warning system.

Team members believe that observed immune responses will serve as an excellent model for understanding how the immune system fights other respiratory pathogens as well. The new information could be used to develop more rapid-acting vaccines or to develop vaccines targeted to flu proteins less prone to change. The project is a large multidisciplinary effort of Stanford researchers.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.