The motivation for this script is that in cloning applications it is often most convenient to number ha sequentially starting with 1 at the first residue. Influenza research database influenza genome database. Human infection with a novel avianorigin influenza a h7n9. Although it was found that a natural compound, stachyflin, inhibited the growth of h1 and h2 but not h3 influenza viruses in mdck cells, inhibitory activity of the compound has not been assessed against h4h16 influenza viruses and the precise mechanism. In the literature, ha is commonly numbered in the h3 numbering scheme for example, as in pdb 4hmg. Influenza hemagglutinin has two mechanisms of helping the virus bind to to the target cell. Molecular basis of the structure and function of h1. Strains of all subtypes of influenza a virus have been isolated from wild birds, although disease is uncommon. Export image and legend, or download trees as newick or phyloxml files for other viewing software. Click on a supported program of interest to go to program description page.
There are 18 known ha subtypes and 11 known na subtypes. Infectious virus recovered from droplets exhaled by ferrets inoculated with this virus contained mutations that conferred restabilisation of ha, indicating the importance of influenza ha stability for betweenhost survival. The protein evolution literature is full of examples of epistatic interactions that enable multiple mutations to access phenotypes not accessible by single mutations 64,65,66. One way is the ha1 globular head domain binds the virus to the sialic acid receptor on the target site, causing the virus and cell to stick together. Human antibodybased immunity to influenza a virus is limited by antigenic drift resulting from amino acid substitutions in the hemagglutinin ha head domain. Oct 09, 2012 these variations are what gives the influenza a viruses their distinct name. Inhibitors based on the presumed transition state intermediate were synthesized that showed good activity in vitro, 1 but bioavailability was found to be a problem and interest lapsed until the crystal structure of na was solved. Influenza a virus hemagglutinin and neuraminidase act as. The opensource code for prediction of influenza protein variants can be found here. Serological testing for detection of antibodies to seasonal influenza viruses is useful for research studies and requires collection of appropriately timed acute and convalescent serum specimens and testing of paired sera at specialized. Is there a rational reason for using such a numbering system, or is this simply an artefact of history. Analysis of known structures of influenza a ha enables us to define amino acids which are structurally and functionally equivalent across all ha subtypes using a numbering.
The study virus aindiatcm 25812019 h9n2 is underlined and marked with a black dot. Bayesian evolutionary tree of influenza ah9n2 virus based on the nucleotide sequence of the ha gene. The influenza virus hemagglutinin head evolves faster than the stalk. Analysis of known structures of influenza a ha enables us to define amino acids which are structurally and functionally equivalent across all ha subtypes using a numbering system based on the mature ha sequence. Therefore, ha is responsible for binding influenza virus to sialic acid on the surface of target cells, such as cells in the upper respiratory tract or erythrocytes, following which event the virus is internalised. Influenza, commonly known as the flu, is an infectious disease caused by an influenza virus. All influenza a viruses were resistant to m2 blockers but both ab viruses were susceptible to oseltamivir and zanamivir.
The numbering is based on the recognition of ha and na through antibodies. A recommended numbering scheme for influenza a ha subtypes david f. Influenza b viruses are not divided into subtypes, but are further broken down into 2 lineages. The ha amino acid sequence of the emerging h5n1 influenza viruses is being. A second function is it catalyzes the entry of viral dna into target cells by membrane fusion 4. Influenza virus infections microbiology three antigenic types of influenza viruses are recognized.
Sep 20, 2009 the main membrane proteins of influenza, the hemagglutinin and the neuraminidase, are the first to be recognized by our immune system. Decoration options let you color tree leaves by metadata. Antigenic characterization of novel h1 influenza a viruses. This is the numbering scheme that is often referred to as the h3 numbering system. Human infection with a novel avianorigin influenza a. Analysis of influenza hemagglutinin from awsn1933h1n1. Characterising viable virus from air exhaled by h1n1. Laboratoryconfirmed avian influenza ah9n2 virus infection.
Equivalent amino acid numbering for subtypes currently circulating. Hemagglutinin is a class i fusion protein, having multifunctional activity as both an attachment factor and membrane fusion protein. Ha subtype numbering conversion influenza research database. Influenza surveillance is necessary for detection of emerging variants of epidemiologic and clinical significance. We describe a group of antibodies that recognize a hitherto unappreciated, conserved site on the ha of h1 subtype. Influenza viruses with h1 ha infect birds, pigs and humans and have caused two of the four pandemics in the past 100 years. A virus containing a mutation destabilising the haemagglutinin ha surface protein displayed reduced survival in air. The other most predominant glycoprotein on the virion surface is na.
The ha protein contained e190, r220, g225, q226, and g228 h3 numbering residues at the receptorbinding pockets, indicating that the virus preferentially binds to the sialic acid2,3neuacgal of the avianlike receptor. How single mutations affect viral escape from broad and. So far, about 3,897 sfs have been defined and mapped in ird for all the proteins of influenza a virus. Use the advanced search to allow you to refine your search with the more fine grained search, and you can pick your viewing options. Influenza viruses bud from the apical surface of polarized epithelial cells e. Similarly, an h5n1 virus has an ha 5 protein and an na 1 protein. Jan 02, 2018 antigenic variation requires frequent revision of annual influenza vaccines. In this report, key clinical and virologic features of. Ha subtype numbering conversion beta this tool allows users to renumber ha sequences according to a crosssubtype numbering scheme proposed by burke and smith in burke df, smith dj. Influenza virus ha subtype numbering conversion tool and the.
Igm, igg, and iga antibody responses to influenza ah1n1. Here are some additional examples of influenza a names in other animals. The immune response tests which will be explained and discussed on an upcoming text were the first to be developed. Structure and classification of influenza virus hemagglutinins ha. We used the nterminal sequence of a mature protein i. The ha protein has 7 potential nglycosylation sites pgss. Antiviral activity of stachyflin on influenza a viruses of. Pdf a recommended numbering scheme for influenza a ha subtypes. Hemagglutinin ha is the major envelope glycoprotein of influenza a and b vir.
Sequence search search for influenza sequences, proteins, and strains using two types of searches. Jun 16, 2014 what exactly is the h3 numbering system. Vipr uses phyml guindon and gascuel, 2003 and offers multiple evolutionary models to infer phylogenies. The ha1 and ha2 polypeptides are numbered as different sequences in this numbering scheme. Epitope mapping of the hemagglutinin molecule of a highly. Jun 06, 2014 recent surveillance data has revealed the emergence of a prominent mutation, e47k ha2 numbering, in the ha2 stalk region of influenza ah1n1pdm09 isolates.
The avian signature showed the largest number of informative. A total of 296 amino acid sequences were aligned by the computer program. A, b, and c the surface proteins hemagglutinin ha and neuraminidase na are the major targets of the protective immune response. The overall strategy to analyze influenza hemagglutinin ha from awsn1933h1n1 is to mutagenize each position of the ha sequence to all possible amino acid variants and use deepsequencing to decipher the amino acid preference at each position. Numbering scheme proposed by david burke and derek smith defining amino acid equivalence across ha subtypes plos one. The emergence of a novel avianorigin influenza a virus strain h7n9 causing severe human disease in china has raised serious concerns. Pdf a recommended numbering scheme for influenza a ha.
Influenza a virus causes influenza in birds and some mammals, and is the only species of the genus alphainfluenzavirus of the virus family orthomyxoviridae. The yearly mutation rate among influenza ha proteins is 1% to 2%, leading to development of new strains of influenza virus that are resistant to previous immunity. As it turns out, the numbering system is really an artefact of history. Annotation program, viral protein annotation program. Here, we report that glycans are added to h1 and h3 has at discrete 5to7year intervals, until they reach a functional glycan. Human influenza a virus hemagglutinin glycan evolution. Jan 07, 2014 this influenza ha stem trimer therefore is an excellent candidate for the design and production of broadly protective influenza vaccines. The pandemic influenza strain, or swine flu, that spread globally in 2009 was referred to as h1n1 and the new bird flu currently h1n1, h5n1, h7n9. A nucleic acid comprising a nucleotide sequence encoding an influenza virus hemagglutinin ha comprising an ha1 domain, wherein said ha1 domain is modified to be free of nlinked glycosylation sites at position 154,165 and 286, a. Positions 145 and 193 h3 numbering, which in h3 hemagglutinin belong to sites a. In this report, key clinical and virologic features of this. A227, g228 amino acids and their numbering as in 1rd8 structure.
Based on the insights gained, we believe that similar procedures can be rapidly developed for the other influenza ha stem domains needed for universal vaccines. Influenza a and b viruses both undergo gradual, continuous change in the ha and na proteins, known as antigenic drift. Origin and evolution of influenza virus hemagglutinin genes. Fifteen different ha antigenic subtypes occur, each subtype crossreacting relatively little with the other subtypes. Amino acid substitutions in internal proteins m, np, ns1 and pb2 were identified. Ha hemagglutinin precursor influenza a virus strain apuerto. A single acute serum specimen for seasonal influenza serology is uninterpretable and should not be collected. Burke and smiths numbering scheme uses analysis of known ha structures to identify amino acids that are structurally and functionally equivalent across all ha. Quick tree produces an accurate topology for 1,000 sequences. Glycan addition can cause large antigenic changes but is limited by fitness costs to viral replication. Numbering for sh1n1 strains containing a deletion outside the receptor.
Apr 11, 2018 influenza a virus can escape antibodies, but it is unclear how the ease of escape depends on the epitope targeted by an antibody. Broad and protective influenza b virus neuraminidase. In humans, h1n1 and h3n2 are the two forms of influenza a the contribute to the normal seasonal flu outbreak. Full text the hemagglutinin of the influenza ah1n1pdm09. Burke and smiths numbering scheme uses analysis of known ha structures to identify amino acids that are structurally and functionally equivalent across all ha subtypes, using a numbering system based on the mature ha sequence.
A recommended numbering scheme for influenza a ha subtypes. Comparisons of residues between subtypes of influenza virus is increasingly used to assess the zoonotic potential of a circulating strain and for comparative. Comparison of amino acid position 4 and 227 h3 numbering in h5 hemagglutinin ha. Igm, igg, and iga antibody responses to ah1n1pdm09 hemagglutinin ha following ah1n1pdm09 virus infection were analyzed to understand antibody isotype responses. Another important caveat is that our experiments examine single aminoacid mutations to the ha from one influenza virus strain. Ha and na reactivities with antibodies define the subtypes of influenza a cox and subbarao 2000. This bayesian tree was generated using the beast software. Structural differences among hemagglutinins of influenza a virus. Nextgeneration vaccine design strategies aim to elicit a broader immunity by directing the human immune response toward conserved sites on the principal viral surface protein, the hemagglutinin ha. Influenza research database influenza genome database with. The influenza neuraminidase na was recognized as a potential drug target in the 1970s. Many different combinations of ha and na proteins are possible. There are at least 16 different ha and nine different na influenza a subtypes zhang.
The novel influenza ah1n1pdm09 virus caused an influenza pandemic in 2009. Search sfs based on amino acid positions, keywords and categories. The mutants are designated by the mab number and in parentheses the clone. The ha regulates the influenza virus entry into the host cell, thus it has a.
The hemagglutinin ha of influenza viruses is a possible target for antiviral drugs because of its key roles in the initiation of infection. Only a few of the 15 antigenic subtypes of influenza a virus hemagglutinin ha. Analysis of known structures of influenza a ha enables us to define amino acids which are structurally and functionally equivalent. The immune response to influenza virus is dominated by the production of hemagglutinin ha antibodies abs. Mar 27, 2017 influenza a virus iav membrane proteins hemagglutinin ha and neuraminidase na are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. Conserved epitope on influenzavirus hemagglutinin head. Production and stabilization of the trimeric influenza. Es2593277t3 new immunization epitope against influenza. A leucine residue at position 4 was deleted in highly pathogenic avian influenza virus ah5n6 isolated in japan during november 2016, compared with the closest relative afelineguangdong12015 h5n6. To answer this question, i did a bit of digging around on the history of the h3 numbering system. Accurate classification and hemagglutinin amino acid signatures for. Influenza research database ha subtype numbering conversion. So, for example, the h1n1 virus has hemagglutinin form 1 and neuraminidase form 1. Shots health news with the new h7n9 virus spreading through china and h5n1 popping up every now and then in southeast asia, its tough to keep track of all.
In certain cases as indicated, residues are numbered in this scheme. Epidemiological and genetic characterization of ph1n1 and. Characterization of highly pathogenic avian influenza virus a. This study describes the epidemiology of influenza types a and b, and molecular characteristics of surface glycoproteins hemagglutinin ha and neuraminidase na of influenza a subtypes. We provide a list of equivalences for amino acids which are known to affect the phenotype of the virus. Comparisons of residues between subtypes of influenza virus is increasingly used to assess the zoonotic potential of a circulating strain and.
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