![CSIRO ScienceImage 354 Influenza Protein Attaching to Cell Membrane](https://upload.wikimedia.org/wikipedia/commons/5/5e/CSIRO_ScienceImage_354_Influenza_Protein_Attaching_to_Cell_Membrane.jpg)
In
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
, hemagglutinins (or ''haemagglutinin'' in
British English
British English (BrE, en-GB, or BE) is, according to Lexico, Oxford Dictionaries, "English language, English as used in Great Britain, as distinct from that used elsewhere". More narrowly, it can refer specifically to the English language in ...
) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion
glycoproteins produced by viruses in the ''
Paramyxoviridae
''Paramyxoviridae'' (from Greek ''para-'' “by the side of” and ''myxa'' “mucus”) is a family of negative-strand RNA viruses in the order '' Mononegavirales''. Vertebrates serve as natural hosts. Diseases associated with this family inclu ...
'' family. Hemagglutinins are responsible for binding to receptors on red blood cells to initiate viral attachment and infection. The
agglutination
In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...
of red cells occurs when
antibodies on one cell bind to those on others, causing amorphous aggregates of clumped cells.Hemagglutinins recognize cell-surface
glycoconjugate
Glycoconjugates are the classification family for carbohydrates – referred to as glycans – which are covalently linked with chemical species such as proteins, peptides, lipids, and other compounds. Glycoconjugates are formed in processes ter ...
s containing sialic acid on the surface of host
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s with a low affinity, and use them to enter the
endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
of host cells. 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.
Agglutination
In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...
and hemagglutinins were discovered by virologist
George K. Hirst in 1941.
Alfred Gottschalk proved in 1957 that hemagglutinins bind a
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
to a host cell by attaching to
sialic acids on
carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...
side chains of
cell-membrane glycoproteins and
glycolipids.
Types
*
Influenza hemagglutinin
Influenza hemagglutinin (HA) or haemagglutinin .html" ;"title="/sup>">/sup> (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 Protei ...
or haemagglutinin: a
homotrimeric
glycoprotein that is found on the surface of
influenza viruses
''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', '' ...
which is responsible for their infectivity.
*
Measles hemagglutinin
Measles hemagglutinin is a hemagglutinin produced by measles virus.
It attaches to CD46 using a dead neuraminidase
Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase t ...
: a hemagglutinin produced by the
measles virus which encodes six structural
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, of which, hemagglutinin and fusion are surface glycoproteins involved in attachment and entry.
*
Parainfluenza hemagglutinin-neuraminidase
Parainfluenza hemagglutinin-neuraminidase is a type of hemagglutinin-neuraminidase
Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and (endo) neuraminidase activity. This is in contrast to the proteins f ...
: a type of
hemagglutinin-neuraminidase
Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and (endo) neuraminidase activity. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins. Its neura ...
produced by
parainfluenza
Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a paraphyletic group of four distinct single-stranded RNA viruses belonging to the '' Paramyxoviridae'' family. These viruses are closely associated wit ...
which is closely associated with both human and veterinary disease.
*
Mumps hemagglutinin-neuraminidase: a kind of hemagglutinin that the mumps virus (MuV) produces, which is the
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
that causes
mumps.
* The PH-E form of
phytohaemagglutinin
Phytohaemagglutinin (PHA, or phytohemagglutinin) is a lectin found in plants, especially certain legumes. PHA actually consists of two closely related proteins, called leucoagglutinin (PHA-L) and PHA-E. These proteins cause blood cells to clump ...
.
Structure
Hemagglutinins are small proteins that project from the virus membrane surface as 135 Å long spikes with a diameter of 30-50 Å. Each spike is made up of three identical monomer subunits, making the protein a
homotrimer. These monomers are formed of two
glycopeptide
Glycopeptides are peptides that contain carbohydrate moieties ( glycans) covalently attached to the side chains of the amino acid residues that constitute the peptide.
Over the past few decades it has been recognised that glycans on cell surfa ...
s, HA1 and HA2, and linked by two disulfide 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. 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
An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis.
A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...
, the fusion domain F, and the membrane anchor subdomain M. The membrane anchor subdomain forms elastic protein chains linking the hemagglutinin to the ectodomain.
Uses in serology
* HIA (''
Hemagglutination Inhibition Assay''): is a serologic assay which can be used either to screen for
antibodies using
RBCs
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...
with known surface
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
s, or to identify RBCs surface antigens such as viruses or bacteria using a panel of known antibodies. This method, performed first by
George K. Hirst in 1942, consists of mixing virus samples with serum dilutions so that antibodies bind to the virus before RBCs are added to the mix. Consequently, those viruses bound to antibodies are unable to link RBCs, meaning that a test’s positive result due to
hemagglutination
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.
Blood ...
has been inhibited. On the contrary, if hemagglutination occurs, the test will result negative.
![Experimental setup to detect hemagglutination](https://upload.wikimedia.org/wikipedia/commons/c/c5/Experimental_setup_to_detect_hemagglutination.png)
* ''Hemagglutination blood typing detection'': this method consists of measuring both blood’s reflectance spectrum alone (non-agglutination), and that of blood mixed with antibody reagents (
agglutination
In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...
) using a waveguide-mode sensor. As a result, some differences in reflectance between the samples are observed. Once
antibodies are added,
blood types and
Rh(D) typing can also be determined thanks to the waveguide-mode sensor. This technique is able to detect weak agglutinations, which are almost impossible to detect with human eyes.
* Using anti-A and anti-B
antibodies that bind specifically to either the A or to the B
blood group
A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates ...
surface
antigens on
RBCs
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...
, it is possible to test a small sample of blood and determine the
ABO
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 43 different blood type (or group) classification system ...
blood group
A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates ...
(or blood type) of an individual. It does not identify the
Rh(D) antigen (Rh blood type).
* The ''bedside card'' method of blood grouping relies on visual
agglutination
In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...
to determine an individual's blood group. The card contains dried blood group antibody
reagents fixed onto its surface. A drop of the individual's blood is placed on each blood group area on the card. The presence or absence of flocculation (visual agglutination) enables a quick and convenient method of determining the
ABO
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 43 different blood type (or group) classification system ...
and
Rhesus status of the individual. As this technique depends on human eyes, it is less reliable than the blood typing based on waveguide-mode sensors.
* The agglutination of red blood cells is used in the
Coombs test
A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood ...
in diagnostic immunohematology to test for
autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of ...
.
* In the case of red blood cells, transformed cells are known as
kodecytes. Kode technology exposes exogenous
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
s on the surface of cells, allowing antibody-antigen responses to be detected by the traditional hemagglutination test.
See also
*
Cold agglutinin disease
Cold agglutinin disease (CAD) is a rare disease, rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below , dir ...
*
Hemagglutination assay
The hemagglutination assay or haemagglutination assay (HA) and the hemagglutination inhibition assay (HI or HAI) were developed in 1941–42 by American virologist George Hirst as methods for quantifying the relative concentration of viruses, bact ...
*
Neuraminidase
Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
: Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glyc ...
*
Influenza hemagglutinin (HA)
*
Agglutination
In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...
References
External links
*
{{Immunologic techniques and tests
Hematology
Immunologic tests