Influenza viruses cause two different epidemiological patterns of infection in human beings: yearly epidemics and periodic pandemics. The yearly epidemics, also called seasonal flu, are responsible for millions of illnesses worldwide and more than 30,000 deaths in the U.S. annually (Reference 3). The available yearly flu vaccines are created to combat seasonal epidemic influenza. Point mutations in predominantly the HA allow influenza viruses to evade the immune responses. This is called antigenic drift, and as a result seasonal influenza vaccines must periodically be updated with new strains in order to provide optimal immunity.
Yearly epidemics cause substantial morbidity and mortality each year, but influenza pandemics are of even greater impact. Influenza pandemics occur when a virus with a new subtype of HA enters an immunologically naive human population. This occurred three times in the last century, and resulted in the pandemics of 1918, 1957, and 1968. The 1918 pandemic resulted in more than 40 million deaths worldwide (Reference 4). (See References 5 and 6 for more information about the 1918 influenza pandemic). The 1957 and 1968 pandemics were not as deadly, but still resulted in significant illness and death. The hemagglutinin subtypes of each pandemic were H1, H2, and H3, respectively.
Influenza viruses that cause pandemics can theoretically arise in multiple ways: direct introduction of an avian virus into the human population, followed by adaptation and human-to-human transmission; avian virus infection and adaptation in an intermediate host (e.g., pigs) followed by introduction into the human population; or genetic reassortment between an avian virus and an existing human/mammalian virus (either in an intermediate host or in human beings directly), resulting in a novel virus capable of infecting humans. (see Figure 2 below).
Until 10 years ago it was believed that avian viruses could not directly infect humans. However, a 1997 outbreak of avian influenza (of the H5N1 subtype) in Hong Kong changed that perception. Ongoing human infections around the world with avian H5N1 viruses have raised substantial concern that these H5N1 viruses may be the source of the next influenza pandemic. Similarly, current evidence suggests that the 1918 pandemic virus arose through introduction of a wholly avian virus into the human population. In contrast, the 1957 and 1968 pandemics arose through reassortment between avian and existing human influenza viruses.
One reason for research interest in swine influenza is the possible role that pigs play in the generation of pandemic influenza viruses. Pigs can be infected by both avian viruses and human viruses, and as such have been postulated as a possible intermediate host in which viruses can reassort (Figure 2). However, pigs may also serve as adaptation hosts in which avian viruses can mutate to become more infectious for humans.
For more information on the roles of pigs in the creation of pandemic influenza viruses, see References 2 and 7 below.
2. Webster, R.G., Bean, W.J., Gorman, O.T., Chambers, T.M., and Kawaoka, Y. 1992. Evolution and ecology of influenza A viruses. Microbiological Reviews 56: 152-79.
3. Thompson, W.W., Shay, D.K., Weintraub, E., Brammer, L., Bridges, C.B., Cox, N.J., Fukuda, K. 2004. Influenza-associated hospitalizations in the United States. Journal of the American Medical Association 292: 1333-1340.
6. Kolata G. 1999. Flu: The Story of the Great Influenza Pandemic of 1918. Farrar Straus & Giroux Publishers, New York, NY.
7. Ito, T., Couceiro, J.N., Kelm, S., Baum, L.G., Krauss, S., Castrucci, M.R., Donatelli, I., Kida, H., Paulson, J.C., Webster, R.G., Kawaoka, Y. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. 1998. Journal of Virology 72: 7367-73.Back to Top