Avian Influenza

Summary

Avian influenza is a disease caused by the influenza A virus, an RNA virus of the family Orthomyxoviridae (‘myxo’ is derived from the Greek word for mucous). Three types of influenza viruses (A, B, and C) are known. These viruses are classified based on the antigenic properties of two viral proteins (matrix and nucleoprotein).  Influenza A is capable of infecting birds and mammals (including humans), whereas Influenza B and C viruses are only known to infect mammals (including humans).

Avian influenza virus (AIV) is a natural disease in wild birds, and all known subtypes of influenza A have been isolated from wild birds.  AIV is generally carried in the gastrointestinal tract and is spread via feces, saliva, and nasal secretions. Most species, however, do not exhibit symptoms of infection.  Poultry and captive birds are more susceptible to AIV and tend to manifest disease symptoms.

There are two basic forms of AIV in bird populations: low-pathogenic (LPAIV) and high-pathogenic (HPAIV). LPAIV is the most common form of virus found in wild birds. Domestic birds, when infected with LPAIV, exhibit mild symptoms of disease.  HPAIV, on the other hand, is not common in wild birds.  Domesticated flocks, however, are particularly susceptible to these strains and experience high mortality. HPAIV is responsible for considerable economic losses, international trade sanctions, and human mortality. Examples of HPAIV include the variants of H5N1 currently circulating in Asia, Africa, and Europe.

Influenza A and Humans

Seasonal flu in humans is caused by a subset of influenza A subtypes (H3N2, H2N2, H1N1, and H1N2).  These viruses can cause respiratory illness with symptoms ranging from mild to severe.  These infections can be passed from human to human via breathing airborne virus particles.

Avian flu in humans is much less common. If a human is infected with AIV the symptoms can range from those typical to seasonal flu to a life-threatening illness. The extent to which humans contract LPAIV is unknown, but since 1997 approximately 200 cases of HPAIV H5N1 have been reported. 

Transmission of AIV from birds to humans requires a fecal oral route, meaning that a human needs to ingest virus shed from a bird in order to be infected.  This can occur if the human lives or works in close proximity to birds or comes in contact with a contaminated surface.  Fortunately, human-to-human transmission of AIV has not been reported. However, AIV is a rapidly evolving group virus; if a strain of HPAIV were to gain the ability to transmit between humans, then it is probable that pandemic flu will occur.

Pandemic flu, or a worldwide epidemic of flu, is characterized as a severe disease caused by a novel strain of influenza that is transmissible between people.  Populations of humans are highly susceptible to infection by novel strains of flu because they have little or no immunity to these strains. During the 20th century, three separate influenza pandemics occurred.  The most devastating of these was the Spanish flu pandemic of 1918, which took the lives of over 50 million people.

Influenza A Biology

The influenza A virion (virus particle) is generally spherical and between 80-120 nm in diameter.  Its genome is made up of eight different pieces of single-stranded RNA, which encode 11 different viral proteins.  Of these proteins, the best characterized are the hemagglutinin (H or HA) and neuraminidase (N or NA) glycoproteins.  Both of these proteins are found on the outside of the virion and are important in infecting host cells and host antigenic response.  Influenza viral subtypes (or serotypes) are identified by the immunological response of antibodies to the combination of H and N proteins on the viral coat.

Influenza A is a rapidly evolving virus because the genome is continually accumulating point mutations.  These mutations are due to the enzyme that is used to replicate the viral genome. This enzyme lacks a proofreading mechanism. This continuous change allows strains of the virus to routinely infect humans even if they have been infected by a similar strain in the past. In terms of evading immune response, the most important virus mutations occur on the H and N surface proteins. The two distinct ways in which influenza A changes its genetic composition and effectively outsmarts the immune system are through antigenic drift and antigenic shift.

Antigenic drift refers to the gradual accumulation of point mutations in the genes that code for the H and N surface proteins. Over time, mutations will accumulate to the point that the specific immunity that a host had developed to an ancestral strain will be insufficient to defend against the evolved descendent of that virus.

Antigenic shift, on the other hand, is when two or more viruses infect the same cell and swap genetic material.  This swapping creates a virus with a novel subtype; this involves major rearrangements of the original H and N surface proteins. Human populations typically have little to no immune protection against the novel strains generated from antigenic shift, making them highly susceptible to infection.

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