Influenzavirus A - Article Avian flu; Bird flu; Bird flu (avian influenza); H5N1
Article: Influenzavirus A
Influenzavirus A is a genus of a family of viruses called Orthomyxoviridae in virus classification. Influenzavirus A has only one species in it; that species is called "Influenza A virus". Influenza A virus causes "avian influenza" (also known as bird flu, avian flu, Influenzavirus A flu, type A flu, or genus A flu). It is hosted by birds, but may infect several species of mammals. All known subtypes are endemic in birds. 
Variants and subtypes
Variants of this species are sometimes named according to the species the strain is endemic in or adapted to. The main variants named using this convention are:
- Bird flu
- Human Flu
- Swine Flu
- Horse Flu
- Dog Flu
Avian 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
The Influenza A virus subtypes are labeled according to an H number (for hemagglutinin) and an N number (for neuraminidase). Each subtype virus has mutated into a variety of strains with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong Flu.
Influenza A viruses are negative sense, single-stranded, segmented RNA viruses. "There are 16 different HA antigens (H1 to H16) and nine different NA antigens (N1 to N9) for influenza A. Until recently, 15 HA types had been recognized, but a new type (H16) was isolated from black-headed gulls caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005." 
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." .
"[C]ontemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host." 
The Influenza A virus genome is contained on eight single (non-paired) RNA strands that code for ten proteins. The segmented nature of the genome allows for the exchange of entire genes between different viral strains when they cohabitate the same cell. 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.
- See H5N1 for the current epizootic (an epidemic in nonhumans) and panzootic (a disease affecting animals of many species especially over a wide area) of H5N1 influenza
Wild fowl act as natural asymptomatic carriers of Influenza A viruses. Prior to the current H5N1 epizootic, strains of Influenza A virus had been demonstrated to be transmitted from wild fowl to only birds, pigs, horses, seals, whales and humans; and only between humans and pigs and between humans and domestic fowl; and not other pathways such as domestic fowl to horse. 
H5N1 has been shown to be also transmitted to tigers, leopards, and domestic cats who were fed uncooked domestic fowl (chickens) with the virus. H3N8 viruses from horses have crossed over and caused outbreaks in dogs. Laboratory mice have been successfully infected with a variety of avian flu genotypes. 
Influenza A viruses spread in the air and in manure and survives longer in cold weather. It can also be transmitted by contaminated feed, water, equipment and clothing; however, there is no evidence that the virus can survive in well-cooked meat. Symptoms in animals vary, but virulent strains can cause death within a few days.
"Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents". 
Avian influenza viruses that the OIE and others test for in order to control poultry disease include: H5N1, H7N2, H1N7, H7N3, H13N6, H5N9, H11N6, H3N8, H9N2, H5N2, H4N8, H10N7, H2N2, H8N4, H14N5, H6N5, H12N5 and others.
- Known outbreaks of highly pathogenic flu in poultry 1959-2003
|1997||New South Wales (Australia)||chicken||H7N4|
|1997||Hong Kong (China)*||chicken||H5N1|
|2002||Hong Kong (China)||chicken||H5N1|
*Outbreaks with significant spread to numerous farms, resulting in great economic losses. Most other outbreaks involved little or no spread from the initially infected farms.
1979: "More than 400 harbor seals, most of them immature, died along the New England coast between December 1979 and October 1980 of acute pneumonia associated with influenza virus, A/Seal/Mass/1/180 (H7N7)." 
1995: "[V]accinated birds can develop asymptomatic infections that allow virus to spread, mutate, and recombine (ProMED-mail, 2004j). Intensive surveillance is required to detect these â€œsilent epidemicsâ€ in time to curtail them. In Mexico, for example, mass vaccination of chickens against epidemic H5N2 influenza in 1995 has had to continue in order to control a persistent and evolving virus (Lee et al., 2004)." 
1997: "Influenza A viruses normally seen in one species sometimes can cross over and cause illness in another species. For example, until 1997, only H1N1 viruses circulated widely in the U.S. pig population. However, in 1997, H3N2 viruses from humans were introduced into the pig population and caused widespread disease among pigs. Most recently, H3N8 viruses from horses have crossed over and caused outbreaks in dogs." 
2000: "In California, poultry producers kept their knowledge of a recent H6N2 avian influenza outbreak to themselves due to their fear of public rejection of poultry products; meanwhile, the disease spread across the western United States and has since become endemic." 
2004: In North America, the presence of avian influenza strain H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. 
2005: Tens of millions of birds died of H5N1 influenza and hundreds of millions of birds were culled to protect humans from H5N1. H5N1 is endemic in birds in southeast Asia and represents a long term pandemic threat.
2006: H5N1 spreads across the globe killing hundreds of millions of birds and over 100 people causing a significant H5N1 impact from both actual deaths and predicted possible deaths.
- Swine flu
- Swine flu (or "pig influenza") refers to varieties of Influenza A virus that affect swine. These include genotypes of H1N1, H1N2 and H3N2.
- Horse flu
- Horse flu (or "Equine influenza") refers to varieties of Influenza A virus that affect horses. Horse 'flu viruses were only isolated in 1956. There are two main types of virus called equine-1 (H7N7) which commonly affects horse heart muscle and equine-2 (H3N8) which is usually more severe.
- Dog flu
- Dog flu (or "canine influenza") refers to varieties of Influenza A virus that affect dogs. The equine influenza virus H3N8 was found to infect and kill greyhound race dogs that had died from a respiratory illness at a Florida racetrack in January 2004.
- H3N8 is now endemic in birds, horses and dogs.
Human influenza virus
Genetic factors in distinguishing between "human flu viruses" and "avian flu viruses" include:
- PB2: (RNA polymerase): Amino acid (or residue) position 627 in the PB2 protein encoded by the PB2 RNA gene. Until H5N1, all known avian influenza viruses had a Glu at position 627, while all human influenza viruses had a lysine.
- HA: (hemagglutinin): Avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors.
Human flu symptoms usually include fever, cough, sore throat, muscle aches, conjunctivitis and, in severe cases, severe breathing problems and pneumonia that may be fatal. The severity of the infection will depend to a large part on the state of the infected person's immune system and if the victim has been exposed to the strain before, and is therefore partially immune.
Highly pathogenic H5N1 avian flu in a human is far worse, killing 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. 
The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human deaths, are:
- H1N1 caused "Spanish Flu"
- H2N2 caused "Asian Flu"
- H3N2 caused "Hong Kong Flu"
- H5N1 is the current pandemic threat
- H7N7 has unusual zoonotic potential
- H1N2 is currently endemic in humans and pigs
- H9N2, H7N2, H7N3, H10N7.
Influenza A virus is the only species in the virus family of Orthomyxoviridae. All known subtypes of Influenza A virus infect birds. Influenza A virus is subdivided into subtypes based on hemagglutinin (H) and neuraminidase (N) protein spikes from the central virus core. There are 16 H types, each with up to 9 N subtypes, yielding a potential for 144 different H and N combinations.
In addition, Influenza A viruses may fall into one of 2 pathotypes: low (LPAI) and high (HPAI) pathogenicity, based on their virulence in poultry populations. Strains of influenza virus A subtypes H5 and H7 are found in both low pathogenic or high pathogenic forms while all other subtypes only have low pathogenic strains.
- A variant of H1N1 was responsible for the Spanish flu pandemic that killed some 50 million to 100 million people worldwide over about a year in 1918 and 1919.  A different variant exists in pig populations. Controversy arose in October, 2005, after the H1N1 genome was published in the journal, Science. Many fear that this information could be used for bioterrorism.
- "When he compared the 1918 virus with today's human flu viruses, Dr. Taubenberger noticed that it had alterations in just 25 to 30 of the virus's 4,400 amino acids. Those few changes turned a bird virus into a killer that could spread from person to person." 
- The Asian Flu was a pandemic outbreak of H2N2 avian influenza that originated in China in 1957, spread worldwide that same year during which a flu vaccine was developed, lasted until 1958 and caused between one and four million deaths.
- H3N2 evolved from H2N2 by antigenic shift and caused the Hong Kong Flu pandemic of 1968 and 1969 that killed up to 750,000.  "An early-onset, severe form of influenza A H3N2 made headlines when it claimed the lives of several children in the United States in late 2003." 
- The dominant strain of annual flu in January 2006 is H3N2. 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. 
- "[C]ontemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host." 
- H5N1 is known for its highly pathogenic strain of Influenza A virus, that is the world's major pandemic threat.
- H7N7 has unusual zoonotic potential. In 2003 in Netherlands 89 people were confirmed to have H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded.
- H1N2 is currently endemic in both human and pig populations. The new H1N2 strain appears to have resulted from the reassortment of the genes of the currently circulating influenza H1N1 and H3N2 subtypes. The hemagglutinin protein of the H1N2 virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase protein is similar to that of the current H3N2 viruses.
- Low pathogenic avian influenza A (H9N2) infection was confirmed in 1999, in China and Hong Kong in two children, and in 2003 in Hong Kong in one child. All three fully recovered. 
- One person in New York in 2003 and one person in Virginia in 2002 were found to have serologic evidence of infection with H7N2. Both fully recovered. 
- In North America, the presence of avian influenza strain H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans with avian influenza have been confirmed in that region. "Symptoms included conjunctivitis and mild influenza-like illness."  Both fully recovered.
- In 2004 in Egypt H10N7 is reported for the first time in humans. It caused illness in two infants in Egypt. One childâ€™s father is a poultry merchant. 
- Bird Flu In India