https://doi.org/10.3390/v11050458, Du R, Cui Q, Rong L. Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry. This linkage preference is a result of structural differences of the hemagglutinin. Together with various forms of a viral antigenic protein called neuraminidase, hemagglutinin is used to distinguish between subtypes of influenza A viruses (e.g., H1N1, H5N1). These subtypes are labeled H1 through H16. A typical influenza virus particle contains some 500 molecules of hemagglutinin and 100 molecules of neuraminidase. Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and neuraminidase activity. HA binds SA through its receptor-binding sites, while NA is a receptor-destroying enzyme by removing SAs. The mechanism of immune protection is more complicated, as while primarily humoral, cell-mediated immunity also plays an essential role in immunity to influenza. Viruses 2019, 11, 458. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513241, Kosik, I.; Yewdell, J.W. Neuraminidase. ... hemagglutinin (HA), and the receptor-destroying enzyme, neuraminidase (NA). … 2018;13(12):e0208028, Lim JW, Na W, Kim HO, Yeom M, Park G, Kang A, Chun H, Park C, Oh S, Le VP, Jeong HH, Song D, Haam S. Cationic Poly(Amino Acid) Vaccine Adjuvant for Promoting Both Cell-Mediated and Humoral Immunity Against Influenza Virus. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The trimeric hemagglutinin glycoprotein acts by promoting attachment of the virus to the host cell surface resulting in fusion and thereby releasing virions into the cytoplasm 9) . pmid:6485252. This binding event is required for internalization of the virus by endocytosis and subsequently the pH-dependent fusion of the viral envelope with the endosomal membrane, ultimately triggering release of the viral RNA into the cytosol. Lehninger’s Principles of Biochemistry, 4th edition, WH Freeman, New York, NY. In addition, a smaller number of matrix (M2) ion channels traverse the lipid envelope. https://doi.org/10.3390/v11050458, Subscribe to receive issue release notifications and newsletters from MDPI journals, You can make submissions to other journals. Although the affinity of this interaction is low, like that of other lectins with their glycan ligands, the avidity is increased by hemagglutinin trimerization and a high density of glycan receptors present on the host cell. [Updated 2019 Oct 8]. The illness caused by the influenza virus can be devastating. The heat inactivation of hemagglutinin resulted in the concomitant loss of neuraminidase. Etymologia: Hemagglutinin and Neuraminidase On This Page Hemagglutinin [heʹmə-glooʹtÄ­-nin] and neuraminidase [noorʹə-minʹĭ-dās] Cite This Article. The function of HA during virus entry has been extensively investigated, however, examination of NA has long been focused to its role in the exit of progeny virus from infected cells, and the role of NA in the entry process is still under-appreciated. See further details. Regarding the induction of immunity, the surface hemagglutinin protein of the influenza virus contains two structural elements, head and stalk wherein the head is the primary target of antibodies that confer protective immunity against influenza viruses 11). Differently combined hemagglutinin (HA) and neuraminidase (NA) antigens are seen in influenza A, that in turn undergo antigenic drifts and shifts resulting in antigenic variation and thereby the necessity for vaccine strain types to vary accordingly. The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7). https://doi.org/10.3390/v11050458, Du, Ruikun; Cui, Qinghua; Rong, Lijun. The Viruses. Virions are a common antigen source for many viral vaccines. The hemagglutinin is also the major antigen against which neutralizing antibodies are produced, and antigenic changes in this protein are in part responsible for new viral outbreaks and considered in formulation of the annual influenza vaccine. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. These subtypes are defined by their interaction with antibodies: all of the variants within a given subtype will be neutralized by a similar set of antibodies. Influenza has three membrane associated proteins; hemagglutinin (HA), neuraminidase (NA), and matrix protein (M). Our dedicated information section provides allows you to learn more about MDPI. RIS [TXT - 2 KB] Article Metrics. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins. Types include: Mumps hemagglutinin-neuraminidase. 1 INTRODUCTION Influenza A virus (IAV) is a continuous burden for human and animal health, and its eradication is near impossible given the wild waterfowl reservoir. The hemagglutinin of the H5N1 virus has been associated with the high pathogenicity of this flu virus strain, apparently due to its ease of conversion to an active form by proteolysis 7). The specificity of the host glycan-hemagglutinin interaction varies considerably for different subtypes of influenza. 1984;137(2):314–23. The name “hemagglutinin” comes from the protein’s ability to cause red blood cells (erythrocytes) to clump together (“agglutinate”) in vitro 1). Available from: https://www.ncbi.nlm.nih.gov/books/NBK537197. Hatta M, Gao P, Halfmann P, Kawaoka Y, 2001. Rationale for vaccination with trivalent or quadrivalent live attenuated influenza vaccines: Protective vaccine efficacy in the ferret model. Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and (endo) neuraminidase EC 3.2.1.18 activity. 2017;91(11). The trimeric hemagglutinin glycoprotein acts by promoting attachment of the virus to the host cell surface resulting in fusion and thereby releasing virions into the cytoplasm 9). The function of hemagglutinin (HA) is to cause red blood cells to cluster together, and it attaches the virus to the infected cell by binding to terminal sialic acid residues on glycoproteins/glycolipids to initiate the infectious cycle 3). J Virol. Roles of the fusion and hemagglutinin-neuraminidase proteins in replication, tropism, and pathogenicity of avian paramyxoviruses. Please note that many of the page functionalities won't work as expected without javascript enabled. Influenza A virus has 18 hemagglutinin (HA), and 11 neuraminidase (NA) subtypes and these antigens are critical for the virulence of the organism 8). those of the individual authors and contributors and not of the publisher and the editor(s). Kalarikkal SM, Jaishankar GB. This requires readjustment of the functional balance of the sialic acid receptor-binding hemagglutinin (HA) and the receptor-destroying neuraminidase (NA) to the sialoglycan-receptor repertoire of the new host. Multiple requests from the same IP address are counted as one view. Influenza Vaccine. Viral sequence analysis revealed three mutations in HA and one in neuraminidase (NA). Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses in Science vol 293, pp1840-1842. PLoS ONE. 2019; 11(5):458. 2019. In this study, a suite of different hemagglutinin and neuraminidase constructs are described, which can be valuable tools to study a wide array of different HAs, NAs and their mutants. Influenza viruses are members of the family Orthomyxoviridae, a group of enveloped viruses containing a segmented negative-sense single-stranded RNA genome. Key words: Influenza A viruses, Neuraminidase, Hemagglutinin, Vaccines, Envelope . Adv Healthc Mater. Jilani TN, Jamil RT, Siddiqui AH. The first influenza pandemic in the new millennium: lessons learned hitherto for current control efforts and overall pandemic preparedness. Please let us know what you think of our products and services. Antigenic drifts are genetic changes occurring in the virus due to various actions of polymerases leading to gradual antigenic changes in both hemagglutinin and neuraminidase producing new variant strains. However, avian influenza viruses bind to receptors expressing Neu5Acα2–3Gal-, and porcine strains bind to both Neu5Acα2–6Gal- and -3Gal-containing receptors. 5, 6 Antigenic shift leads to the emergence of new strains by reassortment between animal and human influenza viruses. All known subtypes of influenza A viruses have been found among birds, except subtype H17N10 and H18N11 which have only been found in bats. We use cookies on our website to ensure you get the best experience. Neuraminidase (NA) helps move the virus particles through the infected cell and assists in budding from host cells by cleaving terminal sialic acids, releasing the virus to complete the infectious cycle 4). An antigenic shift takes place when the currently circulating virus disappears and gets replaced by a new subtype with novel glycoproteins to which antibodies against the previously circulating subtype do not cross-react 10). This review summarizes the current understanding of the roles of HA and NA in relation to each other during virus entry. 4 Influenza virus genome have eight RNA segments and rate of reassortment among co‐infecting viruses can be high. Downloads Article . Trivalent flu vaccines provide protection against two influenza A strains, H1N1 and H3N2, and one influenza B strain. Influenza Hemagglutinin and Neuraminidase: Yin–Yang Proteins Coevolving to Thwart Immunity. 2009 Aug 07;7:2. Neuraminidase (NA) has 11 known subtypes, hence influenza virus is named as H1N1, H5N2 etc., depending on the combinations of HA and NA. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. Parainfluenza hemagglutinin-neuraminidase. Hemagglutinin and neuraminidase are the major surface proteins of this enveloped RNA virus. You seem to have javascript disabled. In: StatPearls [Internet]. Authors to whom correspondence should be addressed. Figures Figure. The last, H16, was discovered only recently on influenza A viruses isolated from black-headed gulls from Sweden and Norway 5). Hemagglutinin (HA) is a viral glycan-binding protein or an antigenic glycoprotein found on the surface of the influenza viruses (as well as many other bacteria and viruses). Author information: (1)Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38101, USA. Glycoproteins . Du, R.; Cui, Q.; Rong, L. Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry. Influenza A viruses (IAVs) occasionally cross the species barrier and adapt to novel host species. Neuraminidase is a glycohydrolase which cleaves the α-ketosidically linked sialic acid (neuraminic acid), 3, off the ends of the glycosidic side chains of hemagglutinin … This finding seems to explain how an H5N1 virus that normally does not infect humans can mutate and become able to efficiently infect human cells. These are studded over the surface of the virus. The hemagglutinin (HA) and neuraminidase (NA) of influenza A virus possess antagonistic activities on interaction with sialic acid (SA), which is the receptor for virus attachment. What does HANA stand for? Influenza vaccine conveys immunity against the influenza virus by stimulating the production of antibodies specific to the disease. Neuraminidase (NA) recognizes the same molecule as hemagglutinin, sialic acid of the cell membrane, but it performs its function in an opposite way, its role is to help the virus to leave the invaded cell.. Neuramidase is needed to remove the acid from the cell and to allow the recently synthesized virus to sprout and invade the next cell. Virology. Sci Rep. 2018 Jul 11;8(1):10432. (adsbygoogle = window.adsbygoogle || []).push({}); (adsbygoogle = window.adsbygoogle || []).push({ Its neuraminidase domain has the CAZy designation glycoside hydrolase family 83 (GH83). I have written about the HA and its function during infection (article one and two ) but not about the neuraminidase (NA, red) or M2 (purple) proteins. Three major hemagglutinin subtypes (H1, H2, and H3) and two neuraminidase subtypes (N1 and N2) have evolved to human species subtypes of influenza A virus. After vaccination, it takes two weeks to build up an immune response against the flu. View Article PubMed/NCBI Google Scholar 59. The first three hemagglutinins, H1, H2, and H3, are found in human influenza viruses. Received: 30 April 2019 / Revised: 17 May 2019 / Accepted: 18 May 2019 / Published: 20 May 2019, (This article belongs to the Special Issue. The hemagglutinin molecule (HA, blue) attaches to cell receptors and initiates the process of virus entry into cells. J Immune Based Ther Vaccines. influenza A virus; hemagglutinin; neuraminidase; virus entry, Help us to further improve by taking part in this short 5 minute survey, West Nile Virus Associations in Wild Mammals: An Update, Conserved Residue Asn-145 in the C-Terminal Heptad Repeat Region of HIV-1 gp41 is Critical for Viral Fusion and Regulates the Antiviral Activity of Fusion Inhibitors, Roles of Hepatitis B Virus Mutations in the Viral Reactivation after Immunosuppression Therapies, Screening of an FDA-Approved Drug Library with a Two-Tier System Identifies an Entry Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus. Role of Neuraminidase in Influenza A(H7N9) Virus Receptor Binding. Rudenko L, Kiseleva I, Krutikova E, Stepanova E, Rekstin A, Donina S, Pisareva M, Grigorieva E, Kryshen K, Muzhikyan A, Makarova M, Sparrow EG, Torelli G, Kieny MP. The most well-studied example of a viral glycan-binding protein is the influenza virus hemagglutinin (HA), which binds to sialic acid–containing glycans on the host cell surface. The paramyxoviruses have two surface glycoproteins, a hemagglutinin-neuraminidase (HN) protein and a fusion (F) protein. Find support for a specific problem on the support section of our website. The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. One limitation to using virions is that the antigen abundance is determined by the content of each protein in the virus. (This is in contrast to the proteins found in influenza, where both functions exist, but in different proteins.) In: StatPearls [Internet]. The serotype of influenza A virus is determined by the Hemagglutinin (HA) and Neuraminidase (NA) proteins present on its surface. The influenza A virion is studded with glycoprotein spikes of hemagglutinin (HA) and neuraminidase (NA), in a ratio of approximately four to one, projecting from a host cell-derived lipid membrane [8]. ↑ Kim SH, Subbiah M, Samuel AS, Collins PL, Samal SK. Robert Daniels' research project "Influenza neuraminidase antigenicity and efficacy in vaccines". Influenza viruses express two types of antigens; hemagglutinin (HA) and neuraminidase (NA). The surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are how the H1N1-Swine flu (a subtype of influenza A virus) is differentiated from other strains of influenza A (H1N1, H1N2) depending on the type of hemagglutinin (HA) or neuraminidase (NA) antigens expressed with metabolic synergy 2). 1959;3:51–61. [31] }); Nelson DL and Cox MM, 2005. "Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry" Viruses 11, no. Influenza virus has been widely used to study the biosynthesis, sorting, distribution, and orientation of membrane proteins. Introduction of these specific mutations into IAV through reverse genetics confirmed their roles in resistance to F10. MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Quadrivalent flu vaccines protect against the same strains as the trivalent vaccine as well as an additional strain of influenza B 12). The best-known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread of influenza infection. Antibodies to neuraminidase act by aggregating viruses on the cell surface effectively and reducing the amount of virus released from infected cells. There are 16 forms of hemagglutinin, designated H1 through H16, associated with influenza type A viruses. Hemagglutinin definition is - an agglutinin (such as an antibody or viral capsid protein) that causes hemagglutination. enable_page_level_ads: true It is responsible for binding the virus to the cell that is being infected. H1N1 Influenza (Swine Flu) [Updated 2019 Jun 9]. Hemagglutinin requires proteolytic cleavage for activation, but because the viral genome does not encode its own protease … Sialobiology of Influenza: Molecular Mechanism of Host Range Variation of Influenza Viruses in Biological and Pharmaceutical Bulletin, vol 28, pp399-408, Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A, 2006. This caveat especially applies to viral-based influenza vaccines where the low abundance of the neuraminidase (NA) surface antigen remains a bottleneck for improving the NA antibody response. Neuraminidase (Sialidase) enzymes are glycoside hydrolase enzymes that cleave (cut) the glycosidic linkages of neuraminic acids.Neuraminidase enzymes are a large family, found in a range of organisms. 5: 458. Kirkpatrick E, Qiu X, Wilson PC, Bahl J, Krammer F. The influenza virus hemagglutinin head evolves faster than the stalk domain. These subtypes are one of … Hemagglutinin (HA) or Haemagglutinin (BE) is an antigenic glycoprotein found on the surface of the influenza viruses. While yearly outbreaks of influenza in the human population induce the development of neutralizing antibody against comm… Additional Resources. Flu shots offer protection against three or four strains of the flu virus. Metric Details. google_ad_client: "ca-pub-9759235379140764", These are small changes (or mutations) in the genes of influenza viruses that can lead to changes in the surface proteins of the virus: HA (hemagglutinin) and NA (neuraminidase). The thermal stability and the effect of guanidine on the hemagglutinin and neuraminidase of three strains of mumps virus were compared. A highly pathogenic avian flu virus of H5N1 type has been found to infect humans at a low rate. Mitnaul LJ(1), Matrosovich MN, Castrucci MR, Tuzikov AB, Bovin NV, Kobasa D, Kawaoka Y. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Influenza A viruses are important pathogens for humans and for many birds and mammals. Benton DJ, Wharton SA, Martin SR, McCauley JW. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China, Shandong Provincial Collaborative Innovation Center for Antiviral Traditional Chinese Medicine, Jinan 250355, China, Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266122, China, Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. under 17 USC 105 and is also made available for use under a CC0 license. Viruses. Influenza A virus has 18 hemagglutinin (HA), and 11 neuraminidase (NA) subtypes and these antigens are critical for the virulence of the organism 8). 2019 Jan;8(2):e1800953. There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes. Franco-Paredes C, Carrasco P, Preciado JI. Three main types of influenza viruses (A, B, and C) infect humans, with influenza A and B viruses causing significant morbidity and mortality annually. The statements, opinions and data contained in the journals are solely Viruses 2019, 11, 346. https://www.mdpi.com/1999-4915/11/4/346, Suzuki, Y, 2005. This is an open access article distributed under the, Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. As with hemagglutinin, neuraminidase comes in a variety of subtypes named N1-N9. Influenza vaccines are the best tool currently available to reduce the risk of influenza infection and associated complications. There are at least 16 different hemagglutinin (HA) antigens. Influenza virus neuraminidase with hemagglutinin activity. The statements, opinions and data contained in the journal, © 1996-2021 MDPI (Basel, Switzerland) unless otherwise stated. It has been reported that single amino acid changes in this avian virus strain’s type H5 hemagglutinin have been found in human patients that “can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses” 6). The effectiveness of a vaccine depends on several host factors such as age, underlying health status, genetic status and furthermore on antigenic matches between the vaccine and circulating viruses 13). Evolution of the receptor binding phenotype of influenza A (H5) viruses in Virology vol 344, issue 2, pp432-8. For additional information, see: Influenza References ↑ Gottschalk A. Chemistry of virus receptors. George Hirst (virologist) and Viral neuraminidase are connected through Mumps rubulavirus, Neuraminidase inhibitor, Hemagglutinin (influenza) and more.. 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Kim SH, Subbiah M, Samuel as, Collins PL, SK... Different hemagglutinin subtypes and 11 different neuraminidase subtypes the current understanding of the hemagglutinin 12 ) MDPI. By reassortment between animal and human influenza viruses are members of the roles of HA NA... Is responsible for binding the virus to the cell that is being infected, J.W TXT - 2 KB Article...: StatPearls Publishing ; 2019 Jan- viral protein that has both hemagglutinin and endo... Virus Receptor binding phenotype of influenza infection ( 5 ) cluster into a bulge in the new millennium: learned... It is responsible for binding the virus and matrix protein ( M ) ), neuraminidase comes in variety. Section provides allows you to learn more about MDPI for a specific on. From infected cells as, Collins PL, Samal SK molecules of neuraminidase virus receptors NY! You get the best experience the journal, © 1996-2021 MDPI ( Basel, Switzerland unless... And human influenza viruses P, Kawaoka Y, 2005 ( be ) is an Antigenic glycoprotein found the! 4 influenza virus can be devastating to F10 MR, Tuzikov AB, NV! Or four strains of influenza-A and -B viruses bind primarily to cells N-acetylneuraminic. Has the CAZy designation glycoside hydrolase family 83 ( GH83 ) shots offer protection against two influenza (. Nucleus and enter this membrane protrusion ( step 6 ) primarily to cells containing acid. Influenza infection 6 ) the vRNA and viral core proteins leave the nucleus and enter this membrane (! ( 2 ): e1800953 viruses express two types of antigens ; hemagglutinin ( HA ) neuraminidase. ( be ) is an Antigenic glycoprotein found on the cell membrane immunity against same... Regard to jurisdictional claims in published maps and institutional affiliations the emergence new... 2019 Jan ; 8 ( 1 ), and orientation of membrane proteins. to! 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