The hemagglutinin protein of influenza a viruses is synthesized as a single polypeptide designated ha0. Investigational hemagglutinintargeted influenza virus. These insights into newly identified ways by which the human immune system can interfere with influenza virus infection may aid the development of novel universal vaccines and antivirals. In addition, influenza a zoonotic viruses are a constant pandemic threat. Influenza viruses belong to the family orthomyxoviridae of enveloped. In vivo, the fusion step is part of the endocytic pathway of influenza virus infection and is triggered by the low ph of the endosomal compartment 6, 7. Structure of the influenza virus hemagglutinin springerlink. The influenza b virus hemagglutinin head domain is less tolerant to transposon mutagenesis than that of the influenza a virus.
Human antibodybased immunity to influenza a virus is limited by antigenic drift resulting from amino acid substitutions in the hemagglutinin ha head domain. Hemagglutinin ha, a glycoprotein of influenza a viruses and its protonchannel m2 are sitespecifically modified with fatty acids. To understand this phenomenon, we passaged virus in mice. Currently, h1n1 and h3n2 viruses are circulating in the human population. Pdf comparative analysis of hemagglutinin of 20 h3n2. Together with various forms of a viral antigenic protein called neuraminidase, hemagglutinin is. Immunology and vaccinepreventable diseases pink book. Influenza viruses are split up into three broad groups known as influenza a, b and c.
Based on receptorbinding analysis and structural studies, song et al. Chimeric hemagglutinin cha constructs and vaccination strategy. Influenza virus hemagglutinin stalkbased antibodies and. Estimates of influenza vaccine effectiveness are also affected by the outcome under study. Aviantohuman receptorbinding adaptation by influenza a. Pdf hemagglutinin of influenza a, but not of influenza b. Rendered in a are three copies of the influenza fusion peptide, which are inserted in the target cell membrane and connected via flexible linkers to the hemagglutinin ectodomain rendered in b. Year in and year out, influenza a virus iav imposes an enormous. This complex is anchored in the viral membrane by three copies of the c. The crystal structure of the uncleaved precursor of the major surface antigen of the. Hemagglutinin definition of hemagglutinin by medical. Review investigational hemagglutinintargeted influenza virus inhibitors liyan zeng a, jie yang and shuwen liua,b aguangdong provincial key laboratory of new drug screening, school of. The designation h1n1 indicates unique traits, which exhibit characteristics that identify the virus to the immune system and allows for attachment and replication of the virus.
Hemagglutinin receptor binding of a human isolate of. Due to the antigenic drift and shift of the virus, seasonal vaccines are. The high variability of the influenza virus genome is reflected by a wide spectrum in host tropism, tissue specificity, and pathogenicity, ranging from local infection. Molecular basis of the structure and function of h1 hemagglutinin of.
Direct visualization of the conformational dynamics of. However, we identified 2 amino acids in avian and human h10, t5 and s186, that are common in circulating human influenza viruses and. Hemagglutinin definition is an agglutinin such as an antibody or viral capsid protein that causes hemagglutination. Influenza virus attaches itself to sialic acids on the surface of epithelial cells of the upper respiratory tract of the host using its own protein hemagglutinin. Hemagglutinin receptor binding avidity drives influenza a. The influenza virus hemagglutinin ha 1 is the virion surface glycoprotein that attaches the virus to its receptors on host cells and fuses the viral envelope with the membranes of endocytic. Abstract the spanish influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Influenza a is the most common type, and h1n1 is a type of influenza a. The pandemic influenza virus 2009 h1n1 was recently introduced into the human population. The 1918 spanish influenza pandemic represents the largest recorded outbreak of any infectious disease.
The influenza virus hemagglutinin viruses from structure. Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of. A, b, c subtypes of type a determined by hemagglutinin and neuraminidase influenza virus strains type amoderate to severe illness all age groups humans and other animals type bmilder disease primarily affects children. Functional balance between neuraminidase and haemagglutinin in. The latter event depends on the exposure of the cleaved hemagglutinin to acid ph and has been documented in detail by experiments on influenza virusinduced hemolysis and cell fusion 15. We formed pseudotyped virions consisting of the hiv1 core and hemagglutinin ha from the avietnam12032004 vn04 h5n1 strain of influenza a virus. The question is not if, but when, a new animal iav will manage to. Influenza a belongs to the orthomyxoviridae family, and is a negative sense singlestranded rna virus which results in respiratory disease. Hemagglutinin, displayed at left, is one of two virallycoded integral envelope proteins of the influenza virus. The world has been aware of the disease and symptoms of influenza for centuries with periodic epidemics recorded in the 19th and 20th centuries. The hemagglutinin ha gene of 2009 h1n1 is derived from classical swine h1n1 virus, which likely shares a common ancestor with the human h1n1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of ha. A mosaic hemagglutininbased influenza virus vaccine.
Species specificity of influenza virus is determined by. Molecular characterizations of surface proteins hemagglutinin and. A, chas consist of a stalk domain from, for example, an h1, h3, or influenza b virus hemagglutinin ha in combination with. In the active form, shown here from pdb entry 1ruz. Influenza a virus hemagglutinin mutations associated with. Influenza a virus hemagglutininneuraminidasereceptor balance. Hemagglutinin is responsible for host cell binding and subsequent fusion of viral and host. Here, we report the complete sequence of the hemagglutinin. The spanish influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. The role of hemagglutinin and neuraminidase in influenza virus. Hemagglutinin is the main immunogen in inactivated influenza vaccines, and its level ie, potency is standardized by single radial immunodiffusion srid. Recombinant influenza a virus hemagglutinin h5 protein.
Influenza has plagued man for centuries and has been described as an unvarying disease caused by a varying virus kilbourne 1975. The two glycoproteins of the influenza virus membrane, hemagglutinin ha 3 and neuraminidase na, both recognize sialic acid 1, 3. Influenza virus hemagglutinin ha contains antigenic sites recognized by the. Influenza virus continues to have a major impact on global health and is responsible for millions of cases of respiratory illness and hundreds of thousands of hospitalizations annually in the. Historically, many studies of influenza vaccine efficacy and effectiveness have used nonspecific outcomes, such. Influenza a virus h5n1 sequences used in the primer design accession number strains. Whereas two cysteines in the short cytoplasmic tail of ha. Human influenza a virus hemagglutinin glycan evolution. Examples of zoonotic influenza include avian influenza, also known as bird flu, with virus subtypes ah5n1 and ah9n2, and swine. Influenza a virus hemagglutinin and neuraminidase act as. How influenza a virus hemagglutinin affects hostspecific virus.
Influenza a virus is an enveloped virus belonging to the orthomyxoviridae family. Predicting the antigenic structure of the pandemic h1n1. A key event in the history of influenza virus biology was the discovery that the hemagglutinin protein had to be cleaved posttranslationally for the virus to be. The influenza virus hemagglutininbinding peptide according to. Influenza hemagglutinin ha or haemagglutinin p british english is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity hemagglutinin is a class i fusion protein, having multifunctional activity as both an attachment factor and membrane fusion protein. In 2017, sixtytwo human infections with influenza ah3n2v virus were reported from nine different states and were closely related to the viruses detected in human. Mechanisms of hemagglutinin targeted influenza virus. Haemagglutinin is an antigenic glycoprotein which allows viral. Two surface proteins of the influenza a virus, hemagglutinin and neuraminidase, play essential roles.
A, b, c subtypes of type a determined by hemagglutinin and neuraminidase influenza virus strains type. For influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin ha, the 3d structure of which is known from xray crystallographic studies. Antihemagglutinin antibody derived lead peptides for. It is a spikeshaped protein that extends from the surface of the virus. Pdf the hemagglutinin ha, the major envelope glycoprotein of influenza, plays an important role during the early stage of infection, and. Pdf roll of hemagglutinin gene in the biology of avian inflenza virus. Virus first isolated in 1933 influenza virus singlestranded rna virus orthomyxoviridae family 3 types. Structure of the uncleaved human h1 hemagglutinin from the. The shift in the receptorbinding specificity of avian influenza virus is critical for the jump from avian to human hosts. Universal influenza virus vaccines that target the. A nanomolar multivalent ligand as entry inhibitor of the. Influenza hemagglutinin and neuraminidase membrane. Influenza virus h1n1 fact sheet morgridge institute for.
The latter event depends on the exposure of the cleaved hemagglutinin to acid ph and has been documented in detail by experiments on influenza virus induced hemolysis and cell fusion 15. Influenza, commonly known as the flu, is an infectious disease caused by an influenza virus. Characterization of h5n1 influenza virus variants with. It frequently affects a large proportion of the population. Origin and evolution of the 1918 spanish influenza virus.
Hemagglutinin is one of the reasons that influenza virus is so effective. Influenza viruses with h1 ha infect birds, pigs and humans and have caused. A change in viral hemagglutinin ha receptor binding specificity from. The efficacy of current antiviral drugs used to treat influenza has been declining because of mutations and resistance of the virus. Influenza a viruses are encoded by eight segments of negativesense rna vrnas, which. Attomolar detection of influenza a virus hemagglutinin. Origin and evolution of the 1918 spanish influenza. These viruses present two major surface glycoproteins. The glycosylation of the influenza a virus hemagglutinin. A multiligand architectural photosensitizer that targets. There are 16 forms of hemagglutinin, designated h1 through h16, associated with influenza type a viruses. Influenza a viruses are dynamically epidemic and genetically diverse.
Hemagglutinin definition of hemagglutinin by merriamwebster. Influenza virus, through cell invasion and propagation with the interaction between hemagglutinin ha present on its surface and glycans on the host cell, causes a rapidly spreading infection throughout the. Ab212054 human4hah5n1hong kong2003 influenza a virusahong kong23h5n1. It can cause annual epidemics and infrequent pandemics. Rapid antigenic evolution in the influenza a virus hemagglutinin precludes effective vaccination with existing vaccines.
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