pneumonia that may be fatal. the severity of the infection will depend in 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. follow-up studies on the impact of statins on influenza virus replication show that pre-treatment of cells with atorvastatin suppresses virus growth in culture. highly pathogenic h5n1 avian influenza in a human is far worse, killing 50% of humans who 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 pandemic deaths, are: h1n1 caused "spanish flu" in 1918 and the 2009 swine flu pandemic h2n2 caused "asian flu" in the late 1950s h3n2 caused "hong kong flu" in the late 1960s h5n1 is considered a global influenza pandemic threat through its spread in the mid-2000s h7n9 is responsible for a 2013 epidemic in china and considered by dr. michael greger, author of how not to die, to have the greatest pandemic threat of the influenza a viruses h7n7 has some zoonotic potential: it has rarely caused disease in humans h1n2 is currently endemic in pigs and has rarely caused disease in humans h9n2, h7n2, h7n3, h5n2, h10n7, h10n3, and h5n8 h1n1 main article: influenza a virus subtype h1n1 human cases and fatalities caused by different influenza a virus subtypesh1n1 was responsible for the 2009 pandemic in both human and pig populations. 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. another variant was named a pandemic threat in the 2009 flu pandemic. controversy arose in october 2005, after the h1n1 genome was published in the journal, science, because of fears that this information could be used for bioterrorism. h1n2 h1n2 is endemic in pig populations and has been documented in a few human cases. h2n2 the asian flu, a pandemic outbreak of h2n2 avian influenza, originated in china in 1957, spread worldwide that same year during which an influenza vaccine was developed, lasted until 1958 and caused between one and four million deaths. h3n2 h3n2 is currently endemic in both human and pig populations. it evolved from h2n2 by antigenic shift and caused the hong kong flu pandemic of 1968, and 1969, that killed up to 750,000. a severe form of the h3n2 virus killed several children in the united states in late 2003. the dominant strain of annual flu in january 2006 was h3n2. measured resistance to the standard antiviral drugs amantadine and rimantadine in h3n2 increased from 1% in 1994 to 12% in 2003 to 91% in 2005. human h3n2 influenza viruses are now endemic in pigs in southern china, where they circulate together with avian h5n1 viruses. h5n1 main article: influenza a virus subtype h5n1 h5n1 influenza a virus subtype h5n1 genetic structure infection human mortality global spread in 2004 in 2005 in 2006 in 2007 social impact pandemic vaccine h5n1 is the world's major influenza pandemic threat. h5n2 japan's health ministry said january 2006 that poultry farm workers in ibaraki prefecture may have been exposed to h5n2 in 2005. the h5n2 antibody titers of paired sera of 13 subjects increased fourfold or more. h5n8 in february 2021, russia reported the first known cases of h5n8 in humans. seven people were confirmed to have been infected in december 2020 and have since recovered. there was no indication of human-to-human transmission. h5n9 a highly pathogenic strain of h5n9 caused a minor flu outbreak in 1966 in ontario and manitoba, canada in turkeys. h7n2 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. h7n3 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. h7n7 h7n7 has unusual zoonotic potential. in 2003 in the netherlands, 89 people were confirmed to have h7n7 influenza virus infection following an outbreak in poultry on several farms. one death was recorded. h7n9 on 2 april 2013, the centre for health protection (chp) of the department of health of hong kong confirmed four more cases in jiangsu province in addition to the three cases initially reported on 31 march 2013. this virus also has the greatest potential for an influenza pandemic among all of the influenza a subtypes. h9n2 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. h10n7 in 2004, in egypt, h10n7 was reported for the first time in humans. it caused illness in two infants in egypt. one child’s father was a poultry merchant. h10n3 in may 2021, in zhenjiang, china h10n3 was reported for the first time in humans. one person was infected. evolution genetic evolution of human and swine influenza viruses, 1918–2009 according to jeffery taubenberger: "all influenza a pandemics since , and indeed almost all cases of influenza a worldwide (excepting human infections from avian viruses such as h5n1 and h7n7), have been caused by descendants of the 1918 virus, including "drifted" h1n1 viruses and reassorted h2n2 and h3n2 viruses. the latter are composed of key genes from the 1918 virus, updated by subsequently incorporated avian influenza genes that code for novel surface proteins, making the 1918 virus indeed the "mother" of all pandemics." researchers from the national institutes of health used data from the influenza genome sequencing project and concluded that during the ten-year period examined, most of the time the hemagglutinin gene in h3n2 showed no significant excess of mutations in the antigenic regions while an increasing variety of strains accumulated. this resulted in one of the variants eventually achieving higher fitness, becoming dominant, and in a brief interval of rapid evolution, rapidly sweeping through the population and eliminating most other variants. in the short-term evolution of influenza a virus, a 2006 study found that stochastic, or random, processes are key factors. influenza a virus ha antigenic evolution appears to be characterized more by punctuated, sporadic jumps as opposed to a constant rate of antigenic change. using phylogenetic analysis of 413 complete genomes of human influenza a viruses that were collected throughout the state of new york, the authors of nelson et al. 2006 were able to show that genetic diversity, and not antigenic drift, shaped the short-term evolution of influenza a via random migration and reassortment. the evolution of these viruses is dominated more by the random importation of genetically different viral strains from other geographic locations and less by natural selection. within a given season, adaptive evolution is infrequent and had an overall weak effect as evidenced from the data gathered from the 413 genomes. phylogenetic analysis revealed the different strains were derived from newly imported genetic material as opposed to isolates that had been circulating in new york in previous seasons. therefore, the gene flow in and out of this population, and not natural selection, was more important in the short term. other animals 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 avian influenza main article: avian influenza 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 wildfowl 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. wild aquatic birds are the natural hosts for a large variety of influenza a viruses. occasionally, viruses are transmitted from these birds to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics. h5n1 has been shown to be transmitted to tigers, leopards, and domestic cats that 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 infected successfully with a variety of avian flu genotypes. influenza a viruses spread in the air and in manure, and survives longer in cold weather. they can also be transmitted by contaminated feed, water, equipment, and clothing; however, there is no evidence the virus can survive in well-cooked meat. symptoms in animals vary, but virulent strains can cause death within a few days. avian influenza viruses that the world organisation for animal health and others test for to control poultry disease include h5n1, h7n2, h1n7, h7n3, h13n6, h5n9, h11n6, h3n8, h9n2, h5n2, h4n8, h10n7, h2n2, h8n4, h14n5, h6n5, and h12n5. known outbreaks of highly pathogenic flu in poultry 1959–2003 year area affected subtype 1959 scotland chicken h5n1 1963 england turkey h7n3 1966 ontario (canada) turkey h5n9 1976 victoria (australia) chicken h7n7 1979 germany chicken h7n7 1979 england turkey h7n7 1983 pennsylvania (us)* chicken, turkey h5n2 1983 ireland turkey h5n8 1985 victoria (australia) chicken h7n7 1991 england turkey h5n1 1992 victoria (australia) chicken h7n3 1994 queensland (australia) chicken h7n3 1994 mexico* chicken h5n2 1994 pakistan* chicken h7n3 1997 new south wales (australia) chicken h7n4 1997 hong kong (china)* chicken h5n1 1997 italy chicken h5n2 1999 italy* turkey h7n1 2002 hong kong (china) chicken h5n1 2002 chile chicken h7n3 2003 netherlands* chicken h7n7 *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. more than 400 harbor seal deaths were recorded in new england between december 1979 and october 1980, from acute pneumonia caused by the influenza virus, a/seal/mass/1/180 (h7n7). swine flu main article: swine influenza swine influenza (or "pig influenza") refers to a subset of orthomyxoviridae that create influenza and are endemic in pigs. the species of orthomyxoviridae that can cause flu in pigs are influenza a virus and influenza c virus, but not all genotypes of these two species infect pigs. the known subtypes of influenza a virus that create influenza and are endemic in pigs are h1n1, h1n2, h3n1 and h3n2. in 1997, h3n2 viruses from humans entered the pig population, causing widespread disease among pigs. 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. the two main types of virus are called equine-1 (h7n7), which commonly affects horse heart muscle, and equine-2 (h3n8), which is usually more severe. h3n8 viruses from horses have infected dogs. 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 – with respiratory illness – greyhound race dogs at a florida racetrack in january 2004. bat flu bat flu (or "bat influenza") refers to the h17n10 and h18n11 influenza a virus strains that were discovered in central and south american fruit bats as well as a h9n2 virus isolated from the egyptian fruit bat. until now it is unclear whether these bat-derived viruses are circulating in any non-bat species and whether they pose a zoonotic threat. initial characterization of the h18n11 subtype, however, suggests that this bat influenza virus is not well adapted to any other species than bats. h3n8 main article: influenza a virus subtype h3n8 h3n8 is now endemic in birds, horses and dogs. subtype list influenza a virus has the following subtypes: influenza a virus subtype h1n1 influenza a virus subtype h1n2 influenza a virus subtype h2n2 influenza a virus subtype h2n3 influenza a virus subtype h3n1 influenza a virus subtype h3n2 influenza a virus subtype h3n8 influenza a virus subtype h5n1 influenza a virus subtype h5n2 influenza a virus subtype h5n3 influenza a virus subtype h5n6 influenza a virus subtype h5n8 influenza