Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates of influenza A virus cause severe disease both in domestic poultry and, rarely, in humans. Occasionally viruses are transmitted from wild aquatic birds to domestic poultry and this may cause an outbreak or give rise to human influenza pandemics.

Influenza A viruses are negative sense, single-stranded, segmented RNA viruses. There are several subtypes, labeled according to an H number (for the type of hemagglutinin) and an N number (for the type of neuraminidase). There are 16 different H antigens (H1 to H16) and nine different N antigens (N1 to N9). The newest H type (H16) was isolated from Black-headed Gulls caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005.

Each virus subtype has mutated into a variety of strains with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species.

A filtered and purified Influenza A vaccine for humans was developed and many countries have stockpiled it to allow a quick administration to the population in the event of an Avian influenza pandemic. Avian influenza is sometimes called avian flu, and commonly bird flu.

Variants and subtypes

Influenza type A viruses are categorized into subtypes based on the type of two proteins on the surface of the viral envelope:

    H = Hemagglutinin, a protein that causes red blood cells to agglutinate.
    N = Neuraminidase, a enzyme that cleaves the glycosidic linkages of the monosaccharide, neuraminic acid

Different influenza viruses encode for different Hemagglutinin and Neuraminidase proteins. For example, the H5N1 virus designates an influenza A subtype that has a type 5 Hemagglutinin (H) protein and a type 1 Neuraminidase (N) protein. There are 16 known types of Hemagglutinin and 9 known types of Neuraminidase, so, in theory, 144 different combinations of these proteins are possible.

Influenza type A viruses are categorized into subtypes based on the type of two proteins on the surface of the viral envelope:

    H = Hemagglutinin, a protein that causes red blood cells to agglutinate.
    N = Neuraminidase, a enzyme that cleaves the glycosidic linkages of the monosaccharide, neuraminic acid

Different influenza viruses encode for different Hemagglutinin and Neuraminidase proteins. For example, the H5N1 virus designates an influenza A subtype that has a type 5 Hemagglutinin (H) protein and a type 1 Neuraminidase (N) protein. There are 16 known types of Hemagglutinin and 9 known types of Neuraminidase, so, in theory, 144 different combinations of these proteins are possible.

Some Variants are identified and named according to the isolate that they are like and thus are presumed to share lineage (example Fujian flu virus like); according to their typical host (example Human flu virus); according to their subtype (example H3N2); and according to their deadliness (example LP, Low Pathogenic). So a flu from a virus similar to the isolate A/Fujian/411/2002(H3N2) is called Fujian flu, human flu, and H3N2 flu.

Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. The main variants named using this convention are:

    * Bird flu
    * Human flu
    * Swine influenza
    * Equine influenza
    * Canine influenza

Variants have also sometimes been named according to their deadliness in poultry, especially chickens:

    * Low Pathogenic Avian Influenza (LPAI)
    * Highly Pathogenic Avian Influenza (HPAI), also called: deadly flu or death flu

Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong flu.

Annual flu

The annual flu (also called "seasonal flu" or "human flu") in the U.S. "results in approximately 36,000 deaths and more than 200,000 hospitalizations each year. In addition to this human toll, influenza is annually responsible for a total cost of over $10 billion in the U.S." The annually updated trivalent influenza vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2, H1N1, and B influenza viruses. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005. Contemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host."

Structure and genetics

"The physical structure of all influenza A viruses is similar. The virions or virus particles are enveloped and can be either spherical or filamentous in form. In clinical isolates that have undergone limited passages in eggs or tissue culture, there are more filamentous than spherical particles, whereas passaged laboratory strains consist mainly of spherical virions." The Influenza A virus genome is contained on eight single (non-paired) RNA strands that code for eleven proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The total genome size is 13,588 bases. The segmented nature of the genome allows for the exchange of entire genes between different viral strains during cellular cohabitation. The eight RNA segments are:

HA encodes hemagglutinin (about 500 molecules of hemagglutinin are needed to make one virion) "The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs."
NA encodes neuraminidase (about 100 molecules of neuraminidase are needed to make one virion).
NP encodes nucleoprotein.
M encodes two matrix proteins (the M1 and the M2) by using different reading frames from the same RNA segment (about 3000 matrix protein molecules are needed to make one virion).
NS encodes two distinct non-structural proteins (NS1 and NEP) by using different reading frames from the same RNA segment.
PA encodes an RNA polymerase.
PB1 encodes an RNA polymerase and PB1-F2 protein (induces apoptosis) by using different reading frames from the same RNA segment.
PB2 encodes an RNA polymerase.

The genome segments have common terminal sequences, and the ends of the RNA strands are partially complementary, allowing them to bond to each other by hydrogen bonds. After transcription from negative-sense to positive-sense RNA the +RNA strands get the cellular 5' cap added by cap snatching, which involves the viral protein NS1 binding to the cellular pre-mRNAs. The cap is then cleaved from the cellular pre-mRNA using a second viral protein, PB2. The short oligo cap is then added to the influenza +RNA strands, allowing its processing as messenger RNA by ribosomes. The +RNA strands also serve for synthesis of -RNA strands for new virions.

The RNA synthesis and its assembly with the nucleoprotein takes place in the cell nucleus, the synthesis of proteins takes place in the cytoplasm. The assembled virion cores leave the nucleus and migrate towards the cell membrane, with patches of viral transmembrane proteins (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and bud through these patches, releasing finished enveloped viruses into the extracellular fluid.

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