1 genetics
1.1 terminology
1.2 genetic structure , related subtypes
1.3 low pathogenic h5n1
1.4 high mutation rate
genetics
the h in h5n1 stands hemagglutinin , depicted in molecular model
the first known strain of hpai a(h5n1) (called a/chicken/scotland/59) killed 2 flocks of chickens in scotland in 1959, strain different current highly pathogenic strain of h5n1. dominant strain of hpai a(h5n1) in 2004 evolved 1999 2002 creating z genotype. has been called asian lineage hpai a(h5n1) .
asian lineage hpai a(h5n1) divided 2 antigenic clades. clade 1 includes human , bird isolates vietnam, thailand, , cambodia , bird isolates laos , malaysia. clade 2 viruses first identified in bird isolates china, indonesia, japan, , south korea before spreading westward middle east, europe, , africa. clade 2 viruses have been responsible human h5n1 infections have occurred during late 2005 , 2006, according who. genetic analysis has identified 6 subclades of clade 2, 3 of have distinct geographic distribution , have been implicated in human infections: map
subclade 1, indonesia
subclade 2, europe, middle east, , africa (called ema)
subclade 3, china
a 2007 study focused on ema subclade has shed further light on ema mutations. 36 new isolates reported here expand amount of whole-genome sequence data available recent avian influenza (h5n1) isolates. before our project, genbank contained 5 other complete genomes europe 2004–2006 period, , contained no whole genomes middle east or northern africa. our analysis showed several new findings. first, european, middle eastern, , african samples fall clade distinct other contemporary asian clades, of share common ancestry original 1997 hong kong strain. phylogenetic trees built on each of 8 segments show consistent picture of 3 lineages, illustrated ha tree shown in figure 1. 2 of clades contain exclusively vietnamese isolates; smaller of these, 5 isolates, label v1; larger clade, 9 isolates, v2. remaining 22 isolates fall third, distinct clade, labeled ema, comprises samples europe, middle east, , africa. trees other 7 segments display similar topology, clades v1, v2, , ema separated in each case. analyses of available complete influenza (h5n1) genomes , of 589 ha sequences placed ema clade distinct major clades circulating in people s republic of china, indonesia, , southeast asia.
terminology
h5n1 isolates identified actual hpai a(h5n1) example, a/chicken/nakorn-patom/thailand/cu-k2/04(h5n1):
a stands genus of influenza (a, b or c).
chicken animal species isolate found in (note: human isolates lack component term , identified human isolates default)
nakorn-patom/thailand place specific virus isolated
cu-k2 laboratory reference number identifies other influenza viruses isolated @ same place , year
04 represents year of isolation 2004
h5 stands fifth of several known types of protein hemagglutinin.
n1 stands first of several known types of protein neuraminidase.
other examples include: a/duck/hong kong/308/78(h5n3), a/avian/ny/01(h5n2), a/chicken/mexico/31381-3/94(h5n2), , a/shoveler/egypt/03(h5n2).
as other avian flu viruses, h5n1 has strains called highly pathogenic (hp) , low-pathogenic (lp). avian influenza viruses cause hpai highly virulent, , mortality rates in infected flocks approach 100%. lpai viruses have negligible virulence, these viruses can serve progenitors hpai viruses. current strain of h5n1 responsible deaths of birds across world hpai strain; other current strains of h5n1, including north american strain causes no disease @ in species, lpai strains. hpai strains identified date have involved h5 , h7 subtypes. distinction concerns pathogenicity in poultry, not humans. normally, highly pathogenic avian virus not highly pathogenic either humans or nonpoultry birds. current deadly strain of h5n1 unusual in being deadly many species, including some, domestic cats, never susceptible influenza virus.
genetic structure , related subtypes
the n in h5n1 stands neuraminidase , protein depicted in ribbon diagram.
h5n1 subtype of species influenza virus of influenzavirus genus of orthomyxoviridae family. other influenza subtypes, h5n1 subtype rna virus. has segmented genome of 8 negative sense, single-strands of rna, abbreviated pb2, pb1, pa, ha, np, na, mp , ns.
ha codes hemagglutinin, antigenic glycoprotein found on surface of influenza viruses , responsible binding virus cell being infected. na codes neuraminidase, antigenic glycosylated enzyme found on surface of influenza viruses. facilitates release of progeny viruses infected cells. hemagglutinin (ha) , neuraminidase (na) rna strands specify structure of proteins medically relevant targets antiviral drugs , antibodies. ha , na used basis naming of different subtypes of influenza viruses. h , n come in h5n1.
influenza viruses significant potential disease , death in humans , other animals. influenza virus subtypes have been confirmed in humans, in order of number of known human pandemic deaths have caused, include:
h1n1, caused 1918 flu pandemic ( spanish flu ) , causing seasonal human flu , 2009 flu pandemic ( swine flu )
h2n2, caused asian flu
h3n2, caused hong kong flu , causes seasonal human flu
h5n1, ( bird flu ), noted having strain (asian-lineage hpai h5n1) kills on half humans infects, infecting , killing species never known suffer influenza viruses before (e.g. cats), being unable stopped culling involved poultry - think due being endemic in wild birds, , causing billions of dollars spent in flu pandemic preparation , preventiveness
h7n7, has unusual zoonotic potential , killed 1 person
h1n2, endemic in humans , pigs , causes seasonal human flu
h9n2, has infected 3 people
h7n2, has infected 2 people
h7n3, has infected 2 people
h10n7, has infected 2 people
h7n9, of feb 2014 has infected 309 people, , lead 70 deaths
low pathogenic h5n1
low pathogenic avian influenza h5n1 (lpai h5n1) called north american h5n1 commonly occurs in wild birds. in cases, causes minor sickness or no noticeable signs of disease in birds. not known affect humans @ all. concern is possible transmitted poultry , in poultry mutate highly pathogenic strain.
1966 - lpai h5n1 a/turkey/ontario/6613/1966(h5n1) detected in flock of infected turkeys in ontario, canada
1975 – lpai h5n1 detected in wild mallard duck , wild blue goose in wisconsin.
1981 , 1985 – lpai h5n1 detected in ducks university of minnesota conducting sampling procedure in sentinel ducks monitored in cages placed in wild short period of time.
1983 – lpai h5n1 detected in ring-billed gulls in pennsylvania.
1986 - lpai h5n1 detected in wild mallard duck in ohio.
2005 - lpai h5n1 detected in ducks in manitoba, canada.
2008 - lpai h5n1 detected in ducks in new zealand.
2009 - lpai h5n1 detected in commercial poultry in british columbia.
in past, there no requirement reporting or tracking lpai h5 or h7 detections in wild birds states , universities tested wild bird samples independently of usda. because of this, above list of previous detections might not inclusive of past lpai h5n1 detections. however, world organization animal health (oie) changed requirement of reporting detections of avian influenza. effective in 2006, confirmed lpai h5 , h7 ai subtypes must reported oie because of potential mutate highly pathogenic strains. therefore, usda tracks these detections in wild birds, backyard flocks, commercial flocks , live bird markets.
high mutation rate
influenza viruses have relatively high mutation rate characteristic of rna viruses. segmentation of genome facilitates genetic recombination segment reassortment in hosts infected 2 different influenza viruses @ same time. uncontagious strain may able pass between humans, 1 of several possible paths pandemic.
the ability of various influenza strains show species-selectivity largely due variation in hemagglutinin genes. genetic mutations in hemagglutinin gene cause single amino acid substitutions can alter ability of viral hemagglutinin proteins bind receptors on surface of host cells. such mutations in avian h5n1 viruses can change virus strains being inefficient @ infecting human cells being efficient in causing human infections more common human influenza virus types. doesn t mean 1 amino acid substitution can cause pandemic, mean 1 amino acid substitution can cause avian flu virus not pathogenic in humans become pathogenic in humans.
influenza virus subtype h3n2 endemic in pigs in china, , has been detected in pigs in vietnam, increasing fears of emergence of new variant strains. dominant strain of annual flu virus in january 2006 h3n2, resistant standard antiviral drugs amantadine , rimantadine. possibility of h5n1 , h3n2 exchanging genes through reassortment major concern. if reassortment in h5n1 occurs, might remain h5n1 subtype, or shift subtypes, h2n2 did when evolved hong kong flu strain of h3n2.
both h2n2 , h3n2 pandemic strains contained avian influenza virus rna segments. while pandemic human influenza viruses of 1957 (h2n2) , 1968 (h3n2) arose through reassortment between human , avian viruses, influenza virus causing spanish flu in 1918 appears entirely derived avian source .
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