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About Viruses

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Human Influenza Viruses

Human influenza viruses are the influenza virus types that circulate among human populations. There are three types of influenza viruses; influenza A virus, influenza B virus, and influenza C virus. Humans can be infected by all three types, although the influenza A virus always present the most serious problems. Influenza A virus may be subtyped according to their composition of two glycoproteins; hemagglutinin (HA, which may be shortened to H) and neuraminidase (NA, which many be shortened to N). Both of these proteins form structures on the surface of the influenza A virus. The HA structure allows the virus to attach to a human body cell and then to enter it. The NA structure helps the newly formed virus to escape the host cell. There are 16 known HA serotypes and 9 known NA serotypes. Thus, there are 153 possible combinations of HA and NA proteins (influenza B and C viruses do not have subtype classifications) based upon this scheme. According to the National Wildlife Health Center, "Within the possible combinations [of HA and NA proteins] are numerous genetic sequences that can determine pathogenicity of the virus to the infected host."

1. All mammals may host the influenza A virus. However, there are large differences between how many and which viral subtypes the many animal species are able to host. The ability of species to host the various influenza virus subtypes is determined by different forms of sialic acid present on the virus HA glycoprotein . Thus, certain species, such as birds, can host all 15 HA serotypes of the influenza A virus, while other species, such as humans, normally can host only three influenza A virus serotypes (H1, H2, and H3).
2. The influenza B virus circulates widely in the human population and can cause both morbidity and mortality among humans. It is usually associated with less severe epidemics than those caused by the influenza A virus, and has not been known to cause a pandemic.
3. The influenza C virus may be found in humans, pigs, and dogs; it causes mild respiratory infection. The influenza C virus is not known to cause epidemics or pandemics.

Presently, there are three types of influenza A viruses circulating in the human population: H1N1, H1N2, and H3N2.

All viruses, including the influenza virus, evolve or undergo mutations that change the character of the surface proteins on the virus. Virus evolution occurs as either antigenic drift or antigenic shift. Antigenic drift happens frequently, usually annually; antigenic shift happens only occasionally, perhaps every 20 - 40 years.

Antigenic drift refers to small, gradual changes that occur through point mutations of the virus' genetic material while the virus replicates itself. In the influenza virus, point mutations occur on the two genes that produce the HA and NA proteins. Mutations are unpredictable and spontaneous, and these changes in the virus surface proteins do not usually result in the appearance of a new virus strain. Because genetic changes occurring as a result of genetic drift tend to be minor, humans who have received earlier flu vaccines or been previously infected by by influenza viruses are likely to retain some degree of immunity against the new virus variant.

Antigenic shift is an infrequent, yet sudden, major change that produces a novel influenza virus, i.e., a virus subtype not previously circulating among the human population. Antigenic shift can occur in a number of ways, one of which is through a process called genetic reassortment. Genetic reassortment happens when different flu virus strains infect the same cell and exchange genetic material.

There are three ways antigenic shift can occur in the influenza A virus:

1. A duck or aquatic bird passes the avian influenza A virus to an intermediate host such as a chicken or a pig. Along those same lines a human passes the human influenza A virus to that same chicken or pig. Genes from both viruses combine and yield a new influenza strain with different H and N proteins. This new strain can pass from the intermediate host to humans who have little to no immunity to the new virus subtype.
2. Without undergoing genetic change, an avian influenza strain can move directly from a duck or other aquatic bird to humans.
3. Without undergoing genetic change, an avian influenza strain can be transmitted directly from a duck or other aquatic bird to an intermediate host such as a chicken or a pig and then to humans.

Usually, the creation of a new influenza virus subtype is followed by severe flu epidemics or pandemics. Given the specificity of the immune response, new influenza viruses are not recognized by antibodies created in response to earlier influenza strains. Humans and other animals who had developed previous immunities to past viruses do not have immunity to new viruses. Consequently, people can get the flu more than once and a new flu vaccine must be produced each year to combat that year's most prevalent strains.

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Avian Influenza Viruses

The natural hosts for avian influenza (influenza A) viruses are certain species of wild birds, usually shorebirds and waterfowl. In natural hosts the virus exists in the gastrointestinal and/or respiratory tract. Infected wild birds disperse the virus through defecation into bodies of water in which the virus can survive for several weeks. Most often wild birds will be affected by low pathogenic avian influenza (LPAI) whose presentation is asymptomatic or mildly symptomatic (e.g., ruffled feathers, drop in egg production, etc.).

Normally, avian influenza viruses do not infect people, so there is little to no immunity to these viruses in the human population. However, three influenza A virus hemagglutinin (HA, which may be shortened to H) subtypes can in fact infect both birds and people: H5, H7, and H9. Beginning in 1997, a H5N1 strain began infecting humans in Hong Kong, and thence spread to Europe and Africa. Since 2003, human H5N1 cases have been documented in Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Thailand, Turkey, and Vietnam. This H5N1 causes highly pathogenic avian influenza (HPAI), which is capable of causing high mortality rates among domestic birds and the rare infected human. Because the HPAI H5N1 is so exceedingly virulent, it is causing worldwide concern.

When a human is infected with the H5N1 strain, he will present with symptoms that are similar to human influenza, including fever, cough, sore throat, muscle aches, and eye infections. However, in over 50% of human cases, symptoms become worse, leading to pneumonia, severe respiratory distress, and other life-threatening complications. More than half of the people infected with the H5N1 virus have died.

The H5N1 virus is not capable of person-to-person spread at this time. In most of the known human H5N1 cases, the virus is believed to have been spread through direct exposure to infected poultry (e.g., domesticated chickens, ducks, and turkeys). However, in 2005, two Vietnamese individuals may have contracted HPAI caused by the H5N1 virus by consuming uncooked duck blood.

Presently, there is no vaccine for H5N1, although researchers throughout the world working on this problem. Scientists are also attempting to increase the present national vaccine production capacity, expand the existing supply, and develop new types of flu vaccines.

Besides vaccines, certain prescription medicines may be useful for alleviating the symptoms of avian influenza in humans. Further, researchers believe that antiviral medications, such as oseltamavir (Tamiflu) and zanamavir (Relenza), help to protect humans from avian influenza (i.e., prevention of illness and/or disease treatment). Unfortunately, due the influenza viruses' high rate of mutation, they can develop resistance against antiviral medications within a short time. For instance, the H5N1 virus is already resistant to amantadine and rimantadine, two antiviral medications commonly used to treat influenza.

The H5N1 virus, which now is endemic to parts of Southeast Asia, is also of significant global concern because of the high economic losses that result when domestic birds become infected with it. In Vietnam, one of the most affected countries, it is estimated that about 44 million birds, or 17% of the total poultry population, were killed in order to limit the spread of the H5N1 virus. The World Bank estimated that the cost to Vietnam's poultry industry was US $120 million (0.3% of GDP). In Indonesia, a survey conducted by the Food and Agriculture Organization indicates that more than 20% of the permanent industrial and commercial farm workers lost their jobs due to avian flu-related impacts. As of today, Cambodia, Indonesia, Laos, and Thailand are the countries that have suffered the most damage from the H5N1 influenza virus. The World Bank estimates that by mid-2005, avian flu had killed more than 140 million birds and caused losses valued at over US $10 billion.

The economic costs of H5N1 have mostly been related to domestic bird deaths, the culling of domestic birds to prevent disease spread, and the costs to governments for avian flu preparedness and prevention. Typically, countries shoulder the burden of economic losses solely, but the benefits from destroying the infected birds are felt at an international scale. Many argue that the international community should contribute aid to help offset the financial costs associated with avian influenza. No one country can protect itself against an influenza pandemic, but the actions one country takes to mitigate its spread can have important implications for the global community.

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Site Last Modified: February 16, 2011

Copyright © 2011 James Martin Center for Nonproliferation Studies (CNS). All Rights Reserved.