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H5N1 genetic structure is the molecular structure of the H5N1 virus's RNA. H5N1 is an Influenza A virus subtype. Experts believe it might mutate into a form that transmits easily from person to person. If such a mutation occurs, it might remain an H5N1 subtype or could shift subtypes as did H2N2 when it evolved into the Hong Kong Flu strain of H3N2. H5N1 has mutated 〔 (Figure 1 ) of the article gives a diagramatic representation of the genetic relatedness of Asian H5N1 hemagglutinin genes from various isolates of the virus.〕 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 that first appeared in China in 1996 in birds and in Hong Kong in 1997 in humans.〔(【引用サイトリンク】 title=H5N1 avian influenza: timeline )〕 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." 〔 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 H5N1 is now the dominant genotype of H5N1. Genotype Z is endemic in birds in southeast Asia and represents a long term pandemic threat. Influenza A viruses have 11 genes on eight separate RNA molecules (): * PB2 (polymerase basic 2) * PB1 (polymerase basic 1) * PB1-F2 (alternate open reading frame near the 5' end of the PB1 gene) * PA (polymerase acidic) * HA (hemagglutinin) * NP (nucleoprotein) * NA (neuraminidase) * M1 and M2 (matrix) * NS1 (non-structural) *NEP/NS2 (nuclear export of vRNPs) Two of the most important RNA molecules are HA and PB1. HA creates a surface antigen that is especially important in transmissibility. PB1 creates a viral polymerase molecule that is especially important in virulence. The HA RNA molecule contains the HA gene, which 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. Humans have avian-type receptors at very low densities and chickens have human-type receptors at very low densities. Some isolates taken from H5N1-infected human have been observed to have HA mutations at positions 182, 192, 223, 226, or 228 and these mutations have been shown to influence the selective binding of the virus to those previously mentioned sialic acid avian and/or human cell surface receptors. These are the types of mutations that can change a bird flu virus into a flu pandemic virus. A 2008 virulence study that mated in a laboratory an avian flu H5N1 virus that circulated in Thailand in 2004 and a human flu H3N2 virus recovered in Wyoming in 2003 produced 63 viruses representing various potential combinations of human and avian influenza A virus genes. One in five were lethal to mice at low doses. The virus that most closely matched H5N1 for virulence was one with the hemagglutinin (HA), the neuraminidase (NA) and the PB1 avian flu virus RNA molecules with their genes combined with the remaining five RNA molecules (PB2, PA, NP, M, and NS) with their genes from the human flu virus. Both the viruses from the 1957 pandemic and 1968 pandemic carried an avian flu virus PB1 gene. The authors suggest that picking up an avian flu virus PB1 gene may be a critical step in a potential flu pandemic virus arising through reassortment."〔(Canadian Press ) article ''Study shows hybrids of bird flu and human flu viruses fit well, could occur'' published June 1, 2008〕 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, () cells to apoptosis. () PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza."〔 This was discovered by Chen ''et al.'' and reported in Nature.〔 "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus."〔(Scientist Live ) article ''A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence'' published October 18, 2007〕 ==Terminology== The Orthomyxovirus family consists of 5 genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus, and Thogotovirus. The "RNA viruses" include the "negative-sense ssRNA viruses" which include 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 called "Influenza A virus"; 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 distinction concerns 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. Both "influenza" (meaning flu) and "A" (meaning species type A) can be used as adjectives of the noun "virus" resulting in the noun phrase "influenza A virus"; which when capitalized is the proper noun Influenza A virus which is the name of the species the noun phrase ''also'' refers to. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「H5N1 genetic structure」の詳細全文を読む スポンサード リンク
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