The H in<unk>  stands for "hemagglutinin", as depicted in this molecular model The first known strain of HPAI A<unk>  (called A/chicken/Scotland/59) killed two flocks of chickens in Scotland in 1959, but that strain was very different from the highly pathogenic strain of<unk> . The dominant strain of HPAI A<unk>  in 2004 evolved from 1999 to 2002 creating the Z genotype. It has also been called "Asian lineage HPAI A<unk> ". Asian lineage HPAI A<unk>  is divided into two antigenic clades. "Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human<unk>  infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections: Map * Subclade 1, Indonesia * Subclade 2, Europe, Middle East, and Africa (called EMA) * Subclade 3, China" A 2007 study focused on the EMA subclade has shed further light on the EMA mutations. "The 36 new isolates reported here greatly expand the amount of whole-genome sequence data available from recent avian influenza <unk>  isolates. Before our project, GenBank contained only 5 other complete genomes from Europe for the 2004–2006 period, and it contained no whole genomes from the Middle East or northern Africa. Our analysis showed several new findings. First, all European, Middle Eastern, and African samples fall into a clade that is distinct from other contemporary Asian clades, all of which share common ancestry with the original 1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show a consistent picture of 3 lineages, as illustrated by the HA tree shown in Figure 1. Two of the clades contain exclusively Vietnamese isolates; the smaller of these, with 5 isolates, we label V1; the larger clade, with 9 isolates, is V2. The remaining 22 isolates all fall into a third, clearly distinct clade, labeled EMA, which comprises samples from Europe, the Middle East, and Africa. Trees for the other 7 segments display a similar topology, with clades V1, V2, and EMA clearly separated in each case. Analyses of all available complete influenza <unk>  genomes and of 589 HA sequences placed the EMA clade as distinct from the major clades circulating in People's Republic of China, Indonesia, and Southeast Asia." Terminology<unk>  isolates are identified like this actual HPAI A<unk>  example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04<unk> : * A stands for the genus of influenza (A, B or C). * chicken is the animal species the isolate was found in (note: human isolates lack this component term and are thus identified as human isolates by default) * Nakorn-Patom/Thailand is the place this specific virus was isolated * CU-K2 is the laboratory reference number that identifies it from other influenza viruses isolated at the same place and year * 04 represents the year of isolation 2004 * H5 stands for the fifth of several known types of the protein hemagglutinin. * N1 stands for the first of several known types of the protein neuraminidase. Other examples include: A/duck/Hong Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and A/shoveler/Egypt/03(H5N2). As with other avian flu viruses,<unk>  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 have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. The strain of<unk>  responsible for the deaths of birds across the world is an HPAI strain; all other strains of<unk> , including a North American strain that causes no disease at all in any species, are LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally, a highly pathogenic avian virus is not highly pathogenic to either humans or nonpoultry birds. This deadly strain of<unk>  is unusual in being deadly to so many species, including some, like domestic cats, never previously susceptible to any influenza virus. Genetic structure and related subtypes Neuraminidase", the protein depicted in this ribbon diagram<unk>  is a subtype of the species Influenza A virus of the genus Alphainfluenzavirus of the family Orthomyxoviridae. Like all other influenza A subtypes, the<unk>  subtype is an RNA virus. It has a segmented genome of eight negative sense, single-strands of RNA, abbreviated as PB2, PB1, PA, HA, NP, NA, MP and NS. HA codes for hemagglutinin, 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. NA codes for neuraminidase, an antigenic glycosylated enzyme found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells. The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies. HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the H and N come from in<unk> . Influenza A viruses are significant for their potential for disease and death in humans and other animals. Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include: * H1N1, which caused the 1918 flu pandemic ("Spanish flu") and the 2009 flu pandemic ("swine flu") and is causing seasonal human flu * H2N2, which caused "Asian flu" * H3N2, which caused "Hong Kong flu" and causes seasonal human flu *<unk> , ("bird flu"), which is noted for having a strain (Asian-lineage HPAI<unk>  that kills over half the humans it infects, infecting and killing species that were never known to suffer from influenza viruses before (e.g. cats), being unable to be stopped by culling all involved poultry—some think due to being endemic in wild birds, and causing billions of dollars to be spent in flu pandemic preparation and preventiveness * H7N7, which has unusual zoonotic potential and killed one person * H1N2, which is endemic in humans and pigs and causes seasonal human flu * H9N2, which has infected three people * H7N2, which has infected two people * H7N3, which has infected two people * H10N7, which has infected two people * H7N9, which as of Feb 2014 has infected 309 people, and lead to 70 deaths Low pathogenic<unk>  Low pathogenic avian influenza<unk>  (LPAI<unk>  also called "North American"<unk>  commonly occurs in wild birds. In most cases, it causes minor sickness or no noticeable signs of disease in birds. It is not known to affect humans at all. The only concern about it is that it is possible for it to be transmitted to poultry and in poultry mutate into a highly pathogenic strain. * 1966 – LPAI<unk>  A/Turkey/Ontario/6613/1966<unk>  was detected in a flock of infected turkeys in Ontario, Canada * 1975 – LPAI<unk>  was detected in a wild mallard duck and a wild blue goose in Wisconsin. * 1981 and 1985 – LPAI<unk>  was detected in ducks by the University of Minnesota conducting a sampling procedure in which sentinel ducks were monitored in cages placed in the wild for a short period of time. * 1983 – LPAI<unk>  was detected in ring-billed gulls in Pennsylvania. * 1986 – LPAI<unk>  was detected in a wild mallard duck in Ohio. * 2005 – LPAI<unk>  was detected in ducks in Manitoba, Canada. * 2008 – LPAI<unk>  was detected in ducks in New Zealand. * 2009 – LPAI<unk>  was detected in commercial poultry in British Columbia. "In the past, there was no requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so states and universities tested wild bird samples independently of USDA. Because of this, the above list of previous detections might not be all inclusive of past LPAI<unk>  detections. However, the World Organization for Animal Health (OIE) recently changed its requirement of reporting detections of avian influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be reported to the OIE because of their potential to mutate into highly pathogenic strains. Therefore, USDA now tracks these detections in wild birds, backyard flocks, commercial flocks and live bird markets." High mutation rate Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different strains of influenza viruses at the same time. A previously uncontagious strain may then be able to pass between humans, one of several possible paths to a pandemic. The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin
Influenza A virus subtype H5N1
Influenza A virus subtype H6N1
Influenza A virus subtype H3N8
Influenza A virus subtype H5N6
Influenza A virus subtype H1N1
Influenza A virus subtype H10N3
SARS-CoV-2 Iota variant
SARS-CoV-2 Alpha variant