Hemagglutinin

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Illustration showing influenza virus attaching to cell membrane via the surface protein hemagglutinin CSIRO ScienceImage 354 Influenza Protein Attaching to Cell Membrane.jpg
Illustration showing influenza virus attaching to cell membrane via the surface protein hemagglutinin

In molecular biology, hemagglutinins (alternatively spelt haemagglutinin, from the Greek haima, 'blood' + Latin gluten, 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the Paramyxoviridae and Orthomyxoviridae families. [1] [2] Hemagglutinins are responsible for binding to receptors on host cells to initiate viral attachment and infection. [3]

Contents

Hemagglutinins recognize cell-surface glycoconjugates containing sialic acid on the surface of host red blood cells with a low affinity and use them to enter the endosome of host cells. [4] In the endosome, hemagglutinins are activated at a pH of 5–6.5 to undergo conformational changes that enable viral attachment through a fusion peptide. [5]

Virologist George K. Hirst discovered agglutination and hemagglutinins in 1941. [6] Alfred Gottschalk proved in 1957 that hemagglutinins bind a virus to a host cell by attaching to sialic acids on carbohydrate side chains of cell-membrane glycoproteins and glycolipids. [7]

The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro . [8]

Types

Structure

Hemagglutinins are small proteins that extend from the surface of the virus membrane as spikes that are 135 Angstroms (Å) in length and 30-50 Å in diameter.. [14] Each spike is composed of three identical monomer subunits, forming the protein a homotrimer. These monomers are formed of two glycopeptides, HA1 and HA2, and linked by two disulphide polypeptides, including membrane-distal HA1 and the smaller membrane-proximal HA2. X-ray crystallography and spectroscopy were used to identify that the majority of the protein structures is made of α-helical proteins. [15] In addition to the homotrimeric core structure, hemagglutinins have four subdomains: the membrane-distal receptor binding R subdomain, the vestigial domain E, that functions as a receptor-destroying esterase, the fusion domain F, and the membrane anchor subdomain M. The membrane anchor subdomain forms elastic protein chains linking the hemagglutinin to the ectodomain. [16]

Uses in serology

A schematic diagram of the experimental setup to detect hemagglutination for blood typing. Experimental setup to detect hemagglutination.png
A schematic diagram of the experimental setup to detect hemagglutination for blood typing.

See also

Related Research Articles

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<span class="mw-page-title-main">Hemagglutinin (influenza)</span> Hemagglutinin of influenza virus

Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.

<i>Orthomyxoviridae</i> Family of RNA viruses including the influenza viruses

Orthomyxoviridae is a family of negative-sense RNA viruses. It includes seven genera: Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in birds and mammals, including humans. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates. The Quaranjaviruses are also arboviruses, infecting vertebrates (birds) and invertebrates (arthropods).

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<i>Measles morbillivirus</i> Species of virus

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<span class="mw-page-title-main">Hemagglutination assay</span> Measure of virus or bacteria concentration

The hemagglutination assay or haemagglutination assay (HA) and the hemagglutination inhibition assay were developed in 1941–42 by American virologist George Hirst as methods for quantifying the relative concentration of viruses, bacteria, or antibodies.

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Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. Viruses that possess HEs include influenza C virus, toroviruses, and coronaviruses of the subgenus Embecovirus. HEs is a dimer transmembrane protein consisting of two monomers, each monomer is made of three domains. The three domains are: membrane fusion, esterase, and receptor binding domains.

Hemagglutination, or haemagglutination, is a specific form of agglutination that involves red blood cells (RBCs). It has two common uses in the laboratory: blood typing and the quantification of virus dilutions in a haemagglutination assay.

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<span class="mw-page-title-main">H5N1 genetic structure</span> Genetic structure of Influenza A virus

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<span class="mw-page-title-main">Virosome</span> Drug or vaccine delivery mechanism

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<i>Murine respirovirus</i> Sendai virus, virus of rodents

Murine respirovirus, formerly Sendai virus (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped, 150-200 nm–diameter, negative sense, single-stranded RNA virus of the family Paramyxoviridae. It typically infects rodents and it is not pathogenic for humans or domestic animals.

<span class="mw-page-title-main">Spike protein</span> Glycoprotein spike on a viral capsid or viral envelope

In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. The proteins are usually glycoproteins that form dimers or trimers.

<span class="mw-page-title-main">Viral neuraminidase</span> InterPro Family

Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins. Viral neuraminidase was discovered by Alfred Gottschalk at the Walter and Eliza Hall Institute in 1957. Neuraminidase inhibitors are antiviral agents that inhibit influenza viral neuraminidase activity and are of major importance in the control of influenza.

<span class="mw-page-title-main">Hemagglutinin-neuraminidase</span>

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<span class="mw-page-title-main">Universal flu vaccine</span> Vaccine that prevents infection from all strains of the flu

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