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Influenza - Avian Flu - Bird Flu

Bird Flu (WHO website: http://www.who.int/csr/don/2004_01_15/en/)
Avian influenza (“bird flu”) and the significance of its transmission to humans
The disease in birds: impact and control measures
Avian influenza is an infectious disease of birds caused by type A strains of the influenza virus. The disease, which was first identified in Italy more than 100 years ago, occurs worldwide.
All birds are thought to be susceptible to infection with avian influenza, though some species are more resistant to infection than others. Infection causes a wide spectrum of symptoms in birds, ranging from mild illness to a highly contagious and rapidly fatal disease resulting in severe epidemics. The latter is known as “highly pathogenic avian influenza”. This form is characterized by sudden onset, severe illness, and rapid death, with a mortality that can approach 100%.
Fifteen subtypes of influenza virus are known to infect birds, thus providing an extensive reservoir of influenza viruses potentially circulating in bird populations. To date, all outbreaks of the highly pathogenic form have been caused by influenza A viruses of subtypes H5 and H7.
Migratory waterfowl – most notably wild ducks – are the natural reservoir of avian influenza viruses, and these birds are also the most resistant to infection. Domestic poultry, including chickens and turkeys, are particularly susceptible to epidemics of rapidly fatal influenza.
Direct or indirect contact of domestic flocks with wild migratory waterfowl has been implicated as a frequent cause of epidemics. Live bird markets have also played an important role in the spread of epidemics.
Recent research has shown that viruses of low pathogenicity can, after circulation for sometimes short periods in a poultry population, mutate into highly pathogenic viruses. During a 1983–1984 epidemic in the United States of America, the H5N2 virus initially caused low mortality, but within six months became highly pathogenic, with a mortality approaching 90%. Control of the outbreak required destruction of more than 17 million birds at a cost of nearly US$ 65 million. During a 1999–2001 epidemic in Italy, the H7N1 virus, initially of low pathogenicity, mutated within 9 months to a highly pathogenic form. More than 13 million birds died or were destroyed.
The quarantining of infected farms and destruction of infected or potentially exposed flocks are standard control measures aimed at preventing spread to other farms and eventual establishment of the virus in a country’s poultry population. Apart from being highly contagious, avian influenza viruses are readily transmitted from farm to farm by mechanical means, such as by contaminated equipment, vehicles, feed, cages, or clothing. Highly pathogenic viruses can survive for long periods in the environment, especially when temperatures are low. Stringent sanitary measures on farms can, however, confer some degree of protection.
In the absence of prompt control measures backed by good surveillance, epidemics can last for years. For example, an epidemic of H5N2 avian influenza, which began in Mexico in 1992, started with low pathogenicity, evolved to the highly fatal form, and was not controlled until 1995.
A constantly mutating virus: two consequences
All type A influenza viruses, including those that regularly cause seasonal epidemics of influenza in humans, are genetically labile and well adapted to elude host defenses. Influenza viruses lack mechanisms for the “proofreading” and repair of errors that occur during replication. As a result of these uncorrected errors, the genetic composition of the viruses changes as they replicate in humans and animals, and the existing strain is replaced with a new antigenic variant. These constant, permanent and usually small changes in the antigenic composition of influenza A viruses are known as antigenic “drift”.
The tendency of influenza viruses to undergo frequent and permanent antigenic changes necessitates constant monitoring of the global influenza situation and annual adjustments in the composition of influenza vaccines. Both activities have been a cornerstone of the WHO Global Influenza Programme since its inception in 1947.
Influenza viruses have a second characteristic of great public health concern: influenza A viruses, including subtypes from different species, can swap or “reassort” genetic materials and merge. This reassortment process, known as antigenic “shift”, results in a novel subtype different from both parent viruses. As populations will have no immunity to the new subtype, and as no existing vaccines can confer protection, antigenic shift has historically resulted in highly lethal pandemics. For this to happen, the novel subtype needs to have genes from human influenza viruses that make it readily transmissible from person to person for a sustainable period.
Conditions favourable for the emergence of antigenic shift have long been thought to involve humans living in close proximity to domestic poultry and pigs. Because pigs are susceptible to infection with both avian and mammalian viruses, including human strains, they can serve as a “mixing vessel” for the scrambling of genetic material from human and avian viruses, resulting in the emergence of a novel subtype. Recent events, however, have identified a second possible mechanism. Evidence is mounting that, for at least some of the 15 avian influenza virus subtypes circulating in bird populations, humans themselves can serve as the “mixing vessel”.
Human infection with avian influenza viruses: a timeline
Avian influenza viruses do not normally infect species other than birds and pigs. The first documented infection of humans with an avian influenza virus occurred in Hong Kong in 1997, when the H5N1 strain caused severe respiratory disease in 18 humans, of whom 6 died. The infection of humans coincided with an epidemic of highly pathogenic avian influenza, caused by the same strain, in Hong Kong’s poultry population.
Extensive investigation of that outbreak determined that close contact with live infected poultry was the source of human infection. Studies at the genetic level further determined that the virus had jumped directly from birds to humans. Limited transmission to health care workers occurred, but did not cause severe disease.
Rapid destruction – within three days – of Hong Kong’s entire poultry population, estimated at around 1.5 million birds, reduced opportunities for further direct transmission to humans, and may have averted a pandemic.
That event alarmed public health authorities, as it marked the first time that an avian influenza virus was transmitted directly to humans and caused severe illness with high mortality. Alarm mounted again in February 2003, when an outbreak of H5N1 avian influenza in Hong Kong caused 2 cases and 1 death in members of a family who had recently travelled to southern China. Another child in the family died during that visit, but the cause of death is not known.
Two other avian influenza viruses have recently caused illness in humans. An outbreak of highly pathogenic H7N7 avian influenza, which began in the Netherlands in February 2003, caused the death of one veterinarian two months later, and mild illness in 83 other humans. Mild cases of avian influenza H9N2 in children occurred in Hong Kong in 1999 (two cases) and in mid-December 2003 (one case). H9N2 is not highly pathogenic in birds.
The most recent cause for alarm occurred in January 2004, when laboratory tests confirmed the presence of H5N1 avian influenza virus in human cases of severe respiratory disease in the northern part of Viet Nam.
Why H5N1 is of particular concern
Of the 15 avian influenza virus subtypes, H5N1 is of particular concern for several reasons. H5N1 mutates rapidly and has a documented propensity to acquire genes from viruses infecting other animal species. Its ability to cause severe disease in humans has now been documented on two occasions. In addition, laboratory studies have demonstrated that isolates from this virus have a high pathogenicity and can cause severe disease in humans. Birds that survive infection excrete virus for at least 10 days, orally and in faeces, thus facilitating further spread at live poultry markets and by migratory birds.
The epidemic of highly pathogenic avian influenza caused by H5N1, which began in mid-December 2003 in the Republic of Korea and is now being seen in other Asian countries, is therefore of particular public health concern. H5N1 variants demonstrated a capacity to directly infect humans in 1997, and have done so again in Viet Nam in January 2004. The spread of infection in birds increases the opportunities for direct infection of humans. If more humans become infected over time, the likelihood also increases that humans, if concurrently infected with human and avian influenza strains, could serve as the “mixing vessel” for the emergence of a novel subtype with sufficient human genes to be easily transmitted from person to person. Such an event would mark the start of an influenza pandemic.
Influenza pandemics: can they be averted?
Based on historical patterns, influenza pandemics can be expected to occur, on average, three to four times each century when new virus subtypes emerge and are readily transmitted from person to person. However, the occurrence of influenza pandemics is unpredictable. In the 20th century, the great influenza pandemic of 1918–1919, which caused an estimated 40 to 50 million deaths worldwide, was followed by pandemics in 1957–1958 and 1968–1969.
Experts agree that another influenza pandemic is inevitable and possibly imminent.
Most influenza experts also agree that the prompt culling of Hong Kong’s entire poultry population in 1997 probably averted a pandemic.
Several measures can help minimize the global public health risks that could arise from large outbreaks of highly pathogenic H5N1 avian influenza in birds. An immediate priority is to halt further spread of epidemics in poultry populations. This strategy works to reduce opportunities for human exposure to the virus. Vaccination of persons at high risk of exposure to infected poultry, using existing vaccines effective against currently circulating human influenza strains, can reduce the likelihood of co-infection of humans with avian and influenza strains, and thus reduce the risk that genes will be exchanged. Workers involved in the culling of poultry flocks must be protected, by proper clothing and equipment, against infection. These workers should also receive antiviral drugs as a prophylactic measure.
When cases of avian influenza in humans occur, information on the extent of influenza infection in animals as well as humans and on circulating influenza viruses is urgently needed to aid the assessment of risks to public health and to guide the best protective measures. Thorough investigation of each case is also essential. While WHO and the members of its global influenza network, together with other international agencies, can assist with many of these activities, the successful containment of public health risks also depends on the epidemiological and laboratory capacity of affected countries and the adequacy of surveillance systems already in place.
While all these activities can reduce the likelihood that a pandemic strain will emerge, the question of whether another influenza pandemic can be averted cannot be answered with certainty.
Clinical course and treatment of human cases of H5N1 avian influenza
Published information about the clinical course of human infection with H5N1 avian influenza is limited to studies of cases in the 1997 Hong Kong outbreak. In that outbreak, patients developed symptoms of fever, sore throat, cough and, in several of the fatal cases, severe respiratory distress secondary to viral pneumonia. Previously healthy adults and children, and some with chronic medical conditions, were affected.
Tests for diagnosing all influenza strains of animals and humans are rapid and reliable. Many laboratories in the WHO global influenza network have the necessary high-security facilities and reagents for performing these tests as well as considerable experience. Rapid bedside tests for the diagnosis of human influenza are also available, but do not have the precision of the more extensive laboratory testing that is currently needed to fully understand the most recent cases and determine whether human infection is spreading, either directly from birds or from person to person.
Antiviral drugs, some of which can be used for both treatment and prevention, are clinically effective against influenza A virus strains in otherwise healthy adults and children, but have some limitations. Some of these drugs are also expensive and supplies are limited.
Experience in the production of influenza vaccines is also considerable, particularly as vaccine composition changes each year to match changes in circulating virus due to antigenic drift. However, at least four months would be needed to produce a new vaccine, in significant quantities, capable of conferring protection against a new virus subtype.
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Details from wikipedia can be followed here: http://en.wikipedia.org/wiki/H5N1

Avian Flu

H5N1 is a subtype of the species called avian influenza virus (bird flu). Avian flu is a disease and avian flu virus is a species. The avian flu virus subtypes are labeled according to an H number and an N number.
The avian influenza 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.
The annual flu (also called "seasonal flu" or "human flu") kills an estimated 36,000 people in the United States each year. The dominant strain of annual flu virus in January 2006 was H3N2 which is now resistant to the standard antiviral drugs amantadine and rimantadine.
Avian influenza virus H3N2 is endemic in pigs ("swine flu") in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. Human influenza viruses can reassort with H5N1 in pigs and mutate into a form which can pass easily among humans. This is one of many possible paths to a pandemic.

Technical
H5N1 is a type of avian influenza virus (bird flu virus) that has mutated[10] through antigenic drift into dozens of highly pathogenic varieties, but all currently belonging to genotype Z of avian influenza virus H5N1. Genotype Z emerged through reassortment in 2002 from earlier highly pathogenic genotypes of H5N1[11] that first appeared in China in 1996 in birds and in Hong Kong in 1997 in humans[12]. The "H5N1 viruses from human infections and the closely related avian viruses isolated in 2004 and 2005 belong to a single genotype, often referred to as genotype Z." [1]
This infection of humans coincided with an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong’s poultry population. This panzootic (a disease affecting animals of many species especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory. The name H5N1 refers to the subtypes of surface antigens present on the virus: hemagglutinin type 5 and neuraminidase type 1.
Genotype Z of avian influenza virus H5N1 is now the dominant genotype of H5N1. Genotype Z is endemic in birds in southeast Asia and represents a long term pandemic threat.
The species called the avian flu virus has a subtype called H5N1 which has a strain called highly pathogenic H5N1 which includes genotype or strain Z which has been divided into two genetic clades which are known from specific isolates. Among H5N1 viruses, only clade one infects humans.
Terminology
"Virus" refers to either the complete virus assemblage or when distinguishing between its parts it refers to the molecules (RNA in the case of H5N1) comprising the genome that is surrounded (encapsidated) by a protective coat of protein called a capsid which binds directly to the viral genome. This complex of protein and nucleic acid is called the nucleocapsid. The complete virus assemblage is referred to as a virion. In normal useage "H5N1 virus" refers to the H5N1 nucleocapsid which is the same as the H5N1 virion since the H5N1 lacks an envelope (a membranous lipid structure that surrounds the nucleocapsid).
Avian influenza is not a genus of Orthomyxoviridae. The term "avian influenza" denotes a disease not a virus. The orthomyxovirus family consists of 5 genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus, and Thogotovirus. Influenzavirus A is not the same as "avian influenza": the former is a genus of viruses, the latter is an illness.
In phylogenetics based taxonomy the "RNA viruses" includes the "negative-sense ssRNA viruses" which includes the Order "Mononegavirales" which includes the Family "Orthomyxoviridae" which contains five genera, classified by variations in nucleoprotein (NP and M) antigens. One of these is the Genus "Influenzavirus A" which consists of a single species (or "type species") called "Influenza A virus" (AI) and one of its subtypes is H5N1.
H5N1 (like the other avian flu viruses) has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). "Avian influenza viruses that cause HPAI are highly virulent, and mortality rates in infected flocks often approach 100%. LPAI viruses are generally of lower virulence, but these viruses can serve as progenitors to HPAI viruses. The current strain of H5N1 responsible for die-offs of domestic birds in Asia is an HPAI strain; other strains of H5N1 occurring elsewhere in the world are less virulent and, therefore, are classified as LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes." The distiction is about pathogenicity in poultry, not humans. Normally a highly pathogenic avian virus is not highly pathogenic to either humans or non-poultry birds. This current strain of H5N1 is unusual in being deadly to so many species.
The species called the avian flu virus has a subtype called H5N1 which has a strain called highly pathogenic H5N1 which includes genotype or strain Z which has been divided into two genetic clades which are known from specific isolates. Only clade one infects humans but all clade one are resistant to adamantanes. Each specific known genetic variation is known from a virus isolate of a specific case of infection.[13]
Influenza virus isolates are notated as in this example: A/New York/348(H1N2):
A stands for the species of influenza (A, B, or C).
New York is the place this specific virus was isolated.
348 is the number of the specimen it was isolated from.
H1 stands for the first of several known types of the protein hemagglutinin.
N2 stands for the second of several known types of the protein neuraminidase.
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H5N1 virus structure
Virus - A virus is one type of microscopic parasite that infects cells in biological organisms.
Orthomyxoviridae - The Orthomyxoviridae are a family of RNA viruses which infect vertebrates. It includes those viruses which cause influenza. Viruses of this family contain 7 to 8 segments of linear negative-sense single stranded RNA.
Influenza virus - "Influenza virus" refers to a subset of Orthomyxoviridae that create influenza. This is not a phylogenetics based taxonomic category.
Avian influenza virus - Avian influenza viruses have 10 genes on eight separate RNA molecules (called: PB2, PB1, PA, HA, NP, NA, M, and NS). HA, NA, and M specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies. This segmentation of the influenza genome facilitates genetic recombination by segment reassortment in hosts who are infected with two different influenza viruses at the same time[1]. Avian influenza viruses compose the Influenzavirus A genus of the Orthomyxoviridae family and are negative sense, single-stranded, segmented RNA viruses.
"The influenza virus RNA polymerase is a multifunctional complex composed of the three viral proteins PB1, PB2 and PA, which, together with the viral nucleoprotein NP, form the minimum complement required for viral mRNA synthesis and replication."[14]
Surface antigen encoding gene segments (RNA molecule): (HA, NA)
HA codes for hemagglutinin which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to cells. This attachment is required for efficient transfer of flu virus genes into cells, a process that can be blocked by antibodies that bind to the hemagglutinin proteins. One genetic factor in distinguishing between human flu viruses and avian flu viruses is that "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."[15] A mutation found in Turkey in 2006 "involves a substitution in one sample of an amino acid at position 223 of the haemoagglutinin receptor protein. This protein allows the flu virus to bind to the receptors on the surface of its host's cells. This mutation has been observed twice before — in a father and son in Hong Kong in 2003, and in one fatal case in Vietnam last year. It increases the virus's ability to bind to human receptors, and decreases its affinity for poultry receptors, making strains with this mutation better adapted to infecting humans." Another mutation in the same sample at position 153 has as yet unknown effects. [16]
NA codes for neuraminidase which is an antigenic glycoprotein enzyme found on the surface of the influenza viruses. It helps the release of progeny viruses from infected cells.
Internal viral protein encoding gene segments (RNA molecule): (M, NP, NS, PA, PB1, PB2)[17]
M codes for the matrix proteins (M1 and M2) that along with the two surface proteins (hemagglutinin and neuraminidase) make up the capsid (protective coat) of the virus. It encodes by using different reading frames from the same RNA segment.
M1 is a protein that binds to the viral RNA.
M2 is a protein that uncoats the virus exposing its contents (the eight RNA segments) to the cytoplasm of the host cell. The M2 transmembrane protein is an ion channel required for efficient infection [18]. The amino acid substitution (Ser31Asn) in M2 some H5N1 genotypes is associated with amantadine resistance[19].
NP codes for nucleoprotein.
NS: NS codes for two nonstructural proteins (NS1 and NEP). "[T]he pathogenicity of influenza virus was related to the nonstructural (NS) gene of the H5N1/97 virus"[20][21]
NS1: Non-structural: nucleus; effects on cellular RNA transport, splicing, translation. Anti-interferon protein. NS1 described in detail. The "NS1 of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia might be responsible for an enhanced proinflammatory cytokine response (especially TNFa) induced by these viruses in human macrophages"[22]. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, the researchers were able to abrogate the effect of the H5N1 NS1. [This] single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus."[23]
NEP: The "nuclear export protein (NEP, formerly referred to as the NS2 protein) mediates the export of vRNPs" [24]
PA codes for the PA protein which is a critical component of the viral polymerase.
PB1 codes for the PB1 protein and the PB1-F2 protein.
The PB1 protein is a critical component of the viral polymerase.
The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment and "interacts with 2 components of the mitochondrial permeability transition pore complex, ANT3 and VDCA1, [sensitizing] cells to apoptosis. [...] PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza."[25] This was discovered by Chen et. al. and reported in Nature[26].
PB2 codes for the PB2 protein which is a critical component of the viral polymerase. 75% of H5N1 human virus isolates from Vietnam had a mutation consisting of Lysine at residue 627 in the PB2 protein; which is believed to cause high levels of virulence.[27][28] Until H5N1, all known avian influenza viruses had a Glu at position 627, while all human influenza viruses had a lysine.
The hemagglutinin, neuraminidase, and M2 proteins are essential viral proteins with functions that can be inhibited by antiviral drugs such as oseltamivir and rimantadine or bound by virus-inactivating antibodies produced by the immune system.
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The H5N1 virus has mutated into a variety of types with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species[29]. The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types[30]. This doesn't mean one amino acid substitution can cause a pandemic but it does mean one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans.
In July 2004, researchers led by H. Deng of the Harbin Veterinary Research Institute, Harbin, China and Professor Robert Webster of the St Jude Children's Research Hospital, Memphis, Tennessee, reported results of experiments in which mice had been exposed to 21 isolates of confirmed H5N1 strains obtained from ducks in China between 1999 and 2002. They found "a clear temporal pattern of progressively increasing pathogenicity"[31]. Results reported by Dr. Webster in July 2005 reveal further progression toward pathogenicity in mice and longer virus shedding by ducks.
Recent research of Taubenberger et al [32] has shown that the 1918 virus, like H5N1, was also an avian influenza virus. Furthermore, Tumpey and colleagues [33] who reconstructed the H1N1 virus of 1918 came to the conclusion that it is was most notably the polymerase genes and the HA and NA genes that caused the extreme virulence of this virus. The sequences of the polymerase proteins (PA, PB1, and PB2) of the 1918 virus and subsequent human viruses differ by only 10 amino acids from the avian influenza viruses. Human forms of seven of the ten amino acids have already been identified in currently circulating H5N1. It is not unlikely that the other mutations eventually will surface and make the H5N1 virus capable of human-to-human transmission. Another important factor is the change of the HA protein to a binding preference for alpha 2,6 sialic acid (the major form in the human respiratory tract). In avian virus the HA protein preferentially binds to alpha 2,3 sialic acid, which is the major form in the avian enteric tract. It has been shown that only a single amino acid change can result in the change of this binding preference. Altogether, only a handful of mutations need to take place in order for H5N1 avian flu to become a pandemic virus like the one of 1918.

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Glossary from Wikipedia

Antigenic drift refers to mutations in the influenza virus that cause changes in the virus's surface proteins over time. Those proteins (hemagglutinin and neuraminidase) are the causes of the body's immune reaction (i.e., they are antigens). Mutations occur almost yearly in the influenza virus, and while the change might not be a major one (which would then be called an antigenic shift), they are sufficient to lessen your body's ability to protect you with antibodies. For this reason, vaccination is required on a yearly basis, with the vaccine adjusted to the new antigen. In influenza, mutations happen frequently because the virus has no way of checking its RNA for errors. Antigenic drift has been responsible for heavier than normal flu seasons in the past, like the outbreak of influenza A Fujian(H3N2) in the 2003 - 2004 flu season. All influenza viruses experience some form of antigenic drift, but it's most pronounced in the influenza A virus. Antigenic drift is not the same as antigenic shift, which is the process by which two different strains of influenza combine to form a new subtype having a mixture of the surface antigens of the two original strains.

Antigenic shift is distinct from antigenic drift, which is a slower mode of genetic change in viruses.
Antigenic shift is the process by which two different strains of influenza combine to form a new subtype having a mixture of the surface antigens of the two original strains. The term antigenic shift is specific to the influenza literature; in other viral systems, the same process is called reassortment or viral shift.
Antigenic shift is contrasted with antigenic drift, which is the natural mutation over time of known strains of influenza (or other things, in a more general sense) to evade the immune system. Antigenic drift occurs in all types of influenza including influenza A, B and C. Antigenic shift, however, occurs only in influenza A because it infects more than just humans. Affected species include other mammals and birds, giving influenza A the opportunity for a major reorganization of surface antigens. Influenza B and C only infect humans, minimizing the chance to mutate drastically

Influenza, commonly known as the flu or the grippe, is a contagious disease of the upper airways and the lungs, caused by an RNA virus of the orthomyxoviridae family. It rapidly spreads around the world in seasonal epidemics, imposing considerable economic burden, in the form of health care costs and lost productivity. Three influenza pandemics in the 20th century, each following a major genetic change in the virus, killed millions of people all over the world.
It is not connected to gastroenteritis, commonly known as "stomach flu" or the "24 hour flu".
The term influenza has its origins in 15th century Italy, where the cause of the disease was ascribed to unfavorable astrological influences. Evolution in medical thought led to its modification to "influenza di freddo", meaning "influence of the cold", which by the 18th century became the prevalent terminology in the English-speaking world as well

The Orthomyxoviridae are a family of RNA viruses which infect vertebrates. It includes those viruses which cause influenza ?
Orthomyxoviridae
Virus classification

Group:
Group V ((-)ssRNA)
Family:
Orthomyxoviridae

Genera
Influenzavirus A
Influenzavirus B
Influenzavirus C
Isavirus
Thogotovirus


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. It was first identified in Italy in the early 1900s and is now known to exist worldwide.

Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus". Influenza B viruses are known to infect humans and seals, giving them influenza. The annually updated trivalent flu vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2, H1N1, and B influenza viruses.

Influenzavirus C is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza C virus". Influenza B viruses are known to infect humans and pigs, giving them influenza. Flu due to the type C species is rare compared to types A or B, but can be severe and can cause local epidemics.

An RNA virus is a virus that either uses ribonucleic acid (RNA) as its genetic material, or whose genetic material passes through an RNA intermediate during DNA replication. For example, Hepatitis B virus is classified as an RNA virus, even though its genome is double-stranded DNA, because the genome is transcribed into RNA during replication. The basis for this classification is error-prone replication of RNA through DNA: All RNA viruses have very high mutation rates because they lack DNA polymerases which can find and edit out mistakes, conducting the equivalent of DNA repair of damaged genetic material. DNA viruses have considerably lower mutation rates. Retroviruses integrate their genome into the host genome, and suffers this problem considerably less.
Although RNA usually mutates rapidly, recent work found that the SARS virus and related RNA viruses contain a gene that mutates very slowly. [1] The gene in question has a complex three-dimensional structure which is hypothesized to provide a chemical function necessary for viral propagation, perhaps as a ribozyme. If so, most mutations would render it unfit for that purpose and would not propagate.
Some RNA viruses:
Arenaviridae
Bunyaviridae
Coronaviridae: SARS
Flaviviridae: Dengue fever - Hepatitis - West Nile virus - Yellow fever
Furovirus
Orthomyxoviridae: Influenza
Paramyxoviridae: Mumps
Picornaviridae: Polio
Pomovirus
Reoviridae
Retroviridae: Human Immunodeficiency Virus
Rhabdoviridae: Rabies - Vesicular stomatitis virus
Tobamovirus: tobacco mosaic virus
Togaviridae
Tymoviridae
Filoviridae: Ebola


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Hemagglutinin (HA) is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. The name hemagglutinin comes from the protein's ability to cause erythrocytes to clump together (Nelson 2005).
Subtypes: - There are at least 16 different HA antigens. These subtypes are labeled H1 through H16. The last, H16, was discovered only recently on influenza A viruses isolated from black-headed gulls from Sweden and Norway (Fouchier 2005). The first three hemagglutinins, H1, H2, and H3, are found in human influenza viruses.
A highly pathogenic avian flu virus of H5N1 type has been found to infect humans at a low rate. It has been reported that single amino acid changes in this avian virus strain's type H5 hemagglutinin have been found in human patients that "can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses" (Gambaryan 2005, Suzuki 2005). This finding seems to explain how an H5N1 virus that normally does not infect humans can mutate and become able to efficiently infect human cells. The hemagglutinin of the H5N1 virus has been associated with the high pathogenicity of this flu virus strain, apparently due to its ease of conversion to an active form by proteolysis (Senne 1996, Hatta 2001).
HA has two primary functions:
1. the recognition of target vertebrate cells, accomplished through the binding of these cells' sialic acid-containing receptors, and
2. the fusion of host and viral endosomal membranes (White 1997), accomplished through the recruitment of HA molecules to the fusion site where some undergo conformational alterations to destabilize the lipid bilayer, thence cooperatively forming a fusion intermediate which associates the two bilayers
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Neuraminidase is an antigenic glycoprotein enzyme (EC 3.2.1.18) found on the surface of the Influenza virus.
Subtype:- Nine neuraminidase subtypes are known; many occur only in various species of duck and chicken. Subtypes N1 and N2 have been positively linked to epidemics in man.
Structure:- The neuraminidase enzyme exists as a mushroom-shape projection on the surface of the influenza virus. It has a head consisting of four co-planar and roughly spherical subunits, and a hydrophobic region that is embedded within the interior of the virus' membrane. It is comprised of a single polypeptide chain that is oriented in the opposite direction to the hemagglutinin antigen. The composition of the polypeptide is a single chain of six conserved polar amino acids, followed by hydrophilic, variable amino acids.
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A glycoprotein is a macromolecule composed of a protein and a carbohydrate (an oligosaccharide). The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. The addition of sugar chains can happen either at asparagine, and is termed N-glycosylation, or at hydroxylysine, hydroxyproline, serine, or threonine, and is termed O-glycosylation. Possible carbohydrates include glucose, glucosamine, galactose, galactosamine, mannose, fucose, and sialic acid.
The sugar group can assist in protein folding or improve its stability. Glycoproteins are often used in proteins that are at least in part located in extracellular space (that is, outside the cell). Glycoproteins are important for immune cell recognition, especially in mammals. Examples of glycoproteins in the immune system are:
molecules such as antibodies (immunoglobulins), which interact directly with antigens
molecules of the major histocompatibility complex (or MHC), which are expressed on the surface of cells and interact with T-cells as part of the adaptive immune response.
Other examples of glycoproteins include:
components of the zona pellucida, which surrounds the oocyte, and is important for sperm-egg interaction.
Soluble glycoproteins often show a high viscosity, for example, in egg white and blood plasma.

Erythrocytes/Red blood cells are the most common type of blood cell and are the vertebrate body's principal means of delivering oxygen from the lungs or gills to body tissues via the blood.Red blood cells are also known as RBCs or erythrocytes (from Greek erythros for "red" and kytos for "hollow", with cyte nowadays translated as "cell"). A schistocyte is a red blood cell undergoing fragmentation, or a fragmented part of a red blood cell.
An antigen is a substance that stimulates an immune response, especially the production of antibodies. Antigens are usually proteins or polysaccharides, but can be any type of molecule, including small molecules (haptens) coupled to a carrier-protein.

posted by Silent Saint @ 11:17 PM