Virus Hemagglutination - an overview (2023)

(1977) detected K virus HAI antibody at prevalence rates of 15–60% with mean antibody titers ranging from 1:13 to 1:21 in four of five colonies examined.

From: Diseases, 1982

Related terms:

Laboratory Diagnosis of Viral Infections

In Fenner's Veterinary Virology (Fifth Edition), 2017

Hemagglutination-Inhibition Assay

For those viruses that hemagglutinate red blood cells of one or another species, such as many of the arthropod-borne viruses, influenza viruses, and parainfluenza viruses, hemagglutination-inhibition assays have been widely used. For detecting and quantitating antibodies in the serum of animals, the methods are sensitive, specific, simple, reliable, and quite inexpensive. In spite of all of the technological advances, hemagglutination inhibition assays remain the mainstay for determining antibody responses to specific influenza A viruses. The principle of the assay is simple—virus binds to red blood cells through receptors on their surface (see Chapter 3: Pathogenesis of Viral Infections and Diseases, Fig. 3.11). Antiviral antibodies bind to these receptors and block hemagglutination. Serum is diluted serially in the wells of the microtiter plate, usually in twofold steps, and to each well a constant amount of virus, usually four or eight hemagglutinating units, is added. The reciprocal of the highest dilution of serum that inhibits the agglutination of the red blood cells by the standardized amount of virus represents the hemagglutination-inhibition titer of the serum (Fig. 5.11). Care should be taken in interpreting many prior sero-surveys based on results of hemagglutination inhibition tests, particularly for paramyxoviruses, as nonspecific inhibitors of agglutination produced many false-positive test results in some of those studies.

Virus Hemagglutination - an overview (1)

Figure 5.11. Hemagglutination inhibition (HI) test for detecting antibodies specific for canine influenza virus (H3N8). Sera treated to remove nonspecific agglutinins and nonspecific inhibitors of agglutination are diluted (twofold) in buffered saline in the wells of a 96-well microtiter plate. Following the dilution operation, an equal volume of canine influenza virus (<4 hemagglutinin units) is added to each well and the plate incubated for 30 minutes. An equal volume of turkey red blood cells (0.5% suspension) is then added to each well. The HI reactions are determined when the control-cell wells show complete settling (button) of the red blood cells. Rows A, B: titration of viral suspension used in test, showing correct amount of hemagglutinin added to test wells. Row C: red blood cell control. Rows D–H: test canine sera. Wells D–H1: test serum control showing no nonspecific agglutination of red blood cells at lowest dilution tested. HI titers are the reciprocal of the last dilution showing inhibition of agglutination by test virus. Row D: HI titer 564; row E: HI titer, 4; row F:HI titer 58; row G: HI titer 52048; row H: HI titer 5 256.

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ENCEPHALITIS VIRUSES (FLAVIVIRIDAE) | Tick-Borne Encephalitis And Wesselsbron Viruses

E.A. Gould, in Encyclopedia of Virology (Second Edition), 1999

Immune Response

Infection with a TBE complex virus stimulates antibodies against each of the recognized structural and nonstructural proteins. The predominant protective antibodies are those stimulated by the E and NS1 proteins. Antibodies against the E protein neutralize virus infectivity, inhibit virus hemagglutination and are generally crossreactive with TBE complex and other flaviviruses in nonfunctional tests such as ELISA or immunofluorescence microscopy. NS1-specific antibodies are less broadly crossreactive with non-TBE complex flaviviruses. Nonfatal infections by TBE complex viruses induce long-lasting immunity to reinfection with TBE complex-related viruses but there is insufficient information to predict the extent to which crossprotection occurs amongst more distantly related mosquito-transmitted flaviviruses. Conventionally, immune animals are not thought to be hosts for virus transmission by infected vectors; however, there is experimental evidence of TBE virus transmission by ticks cofeeding on immune rodents.

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In Fenner's Veterinary Virology (Fifth Edition), 2017


Clinical signs, hematological changes, and postmortem findings are characteristic and sufficient for presumptive diagnosis of feline panleukopenia. The usual confirmatory tests include either antigen-capture enzyme immunoassay or immunofluorescence for the detection of antigen in tissues, or PCR assay for the detection of viral DNA in feces or tissues. Virus isolation or hemagglutination assays also can be used. Serologic diagnosis is by hemagglutination-inhibition assays, ELISA, or indirect immunofluorescence. Positive PCR results should be carefully interpreted in the absence of other confirmation, and quantitative PCR showing high levels of viral DNA can be useful to confirm an active infection. The viral DNA may persist at low levels in tissues for months (or perhaps years) in the absence of active viral replication. Truly persistent shedding of DNA in feces is not generally seen.

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Laboratory Diagnosis of Virus Diseases

Christopher J. Burrell, ... Frederick A. Murphy, in Fenner and White's Medical Virology (Fifth Edition), 2017

Diagnosis of Acute Infection by Demonstrating a Rise in Antibody

Following the traditional approach, “paired sera” are taken from the patient, the “acute-phase” serum sample as early as possible in the illness and the “convalescent-phase” sample at least 10 to 14 days later. Blood is collected in the absence of anticoagulants and given time to clot, and then the serum is separated. Acute and convalescent serum samples should be tested simultaneously. For certain tests that measure inhibition of some biological function of a virus, for example, virus neutralization or hemagglutination-inhibition, the sera must first be inactivated by heating at 56°C for 30 minutes and sometimes treated by additional methods, in order to destroy various types of non-specific inhibitors of infectivity or hemagglutination, respectively. Prior treatment of the serum is not generally required for assays that simply measure antigen–antibody binding, such as EIA, RIA, Western blot, latex agglutination, immunofluorescence, or immunodiffusion.

The paired sera are then titrated for antibodies using any of a wide range of available serological techniques. Demonstration of a significant rise in antibody titer (conventionally, a four-fold rise when titrating the test serum as two-fold dilutions) is taken as proof of “seroconversion,” that is, acute infection with the agent in question. In practice, there are many subtleties in the interpretation of results. For example, the timing of the collection of the paired sera in relation to the date of onset of illness must be carefully assessed to allow for inappropriate sample timing. Moreover, an individual with immunity due to prior infection or immunization may undergo a second or reinfection, often of a subclinical nature, but showing a rise in antibody titer. It is obvious that in reality, two well-timed paired sera to allow demonstration of a four-fold rise in titer, are often not available. Attempts are sometimes made to infer that a recent infection has occurred, on the basis of one serum sample containing a relatively high antibody titer; indeed laboratories may issue guidelines about what titer of antibody in a single serum may imply recent infection. In practice this is often unreliable, as the peak antibody titer seen in the convalescent stage of an infection can vary significantly from person to person.

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The Flaviviruses: Detection, Diagnosis, and Vaccine Development

Goro Kuno, in Advances in Virus Research, 2003

a. Hemagglutination-Inhibition Test

The procedure adopted for microtitration (Sever, 1962) of the original protocol (Clarke and Casals, 1958) has been widely used for a variety of objectives, ranging from case diagnosis to serosurvey.

The principle of this test is based on the propensity of most arboviruses to aggregate erythrocytes of certain animals. If, however, virus is mixed with a serum specimen containing an antibody against the virus, hemagglutination is abrogated, the highest serum dilution causing the inhibition corresponding to the antibody concentration in the specimen. Because hemagglutination is pH dependent, selection of an optimal pH is critical.

The major advantages of the this test are (i) it does not require expensive equipment or instruments and (ii) it is highly useful to initially screen etiologic agents at the major group level because of its extensive and exclusive cross-reaction to all members of one virus group (antigenic complex, genus, or family) and excellent ability to segregate that group from others.

Although it has been sometimes erroneously believed to be an IgG assay, actually it measures other immunoglobulins, such as IgM and IgA, as well. Kaolin treatment of serum specimens for removal of nonspecific inhibitors still leaves a considerable amount of HI-reactive IgM (Granström et al., 1978; Wiemers and Stallman, 1975), although it was once thought to remove it (Mann et al., 1967).

For the visualization of agglutination, goose erythrocytes have been used in most laboratories. Other investigators have found trypsinized human type “O” blood cells or goose cells preserved with formalin treatment useful in laboratories where fresh goose blood cells are difficult to procure (Ahandrik et al., 1986). As for antigen, sucrose-acetone extracts of infected suckling mouse brains were popularly used in the past, but some of them have been replaced with antigens prepared from infected cell cultures. More recently, recombinant antigens, such as Japanese encephalitis (JE) viral antigen expressed as extracellular subviral particles, became available. However, although some recombinants had a hemagglutination activity (Heinz et al., 1995; Hunt et al., 2001; Konishi et al., 1996), other recombinant antigens either have not been evaluated for utility in the HI test or were found to be nonreactive (Davis et al., 2001; Konishi et al., 2001). Availability of a good HI-reactive recombinant antigen for the diagnoses of West Nile fever (WNF) and other viral infections in wildlife is important, because an HI test with such a safe antigen obviates development of antispecies antibodies necessary in the popular ELISA but currently unavailable commercially.

Although HI antibodies in neurotropic flaviviral infections, compared with those of non-neurotropic infections, are sometimes detectable within 3 to 5 days after the onset of illness because of longer intervals between infection and development of symptoms; generally, a disadvantage of this test is that for case diagnosis it is essentially a retrospective diagnostic test because both acute phase and convalescent phase specimens must be obtained to determine a significant change in antibody titer. Many recovered former patients do not feel a strong need to return to clinics for second blood samples; thus, unless convalescent phase specimens are actively sought by physicians or diagnostic laboratories, many cases with only acute phase specimens would remain inconclusive. Furthermore, it is one of the most cross-reactive tests to flavivirus. It should also be remembered that in the microHI test, which is the standard today, titers obtained are often lower compared with those by the macroHI test (Akov, 1976).

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Viral Diseases of the Respiratory System

John C. Parker, Conrad B. Richter, in Diseases, 1982

C Epizootiology

1 Host Range

K virus infects laboratory-reared and feral mice (Mus musculus) exclusively. Young suckling mice of either sex and all strains tested, including C3H, C57BL, A, C, and Swiss, have been susceptible to lethal infection (Kilham, 1952; Holt, 1959). Attempts to infect embryonated eggs, suckling rabbits, suckling and adult hamsters, adult guinea pigs, suckling albino rats, meadow mice (Microtus), and deer mice (Peromyscus) have been unsuccessful (Kilham, 1952; Holt, 1959). All ages of mice are susceptible to infection; however, lethal infection occurs only in suckling mice up to approximately 8 days of age. Between 8 and 18 days of age, resistance to lethal infection becomes complete (Kilham and Murphy, 1953; Holt, 1959).

2 Prevalence and Geographic Distribution

K virus infection in mice has been reported in the United States (Kilham, 1952; Rowe et al., 1962; Parker, 1973; Parker et al., 1966), Canada (Descoteaux et al., 1977), Germany (Kraus et al., 1968), and Australia (Derrick and Pope, 1960; Holt, 1959), and therefore probably occurs worldwide.

Prevalence of infection within colonies from different geographic areas is not fully understood, perhaps due partly to insensitive diagnostic techniques and partly to a lack of knowledge of the biology of the normal chronic latent infection. The results of serologic surveys by Rowe et al. (1962) using the CF test showed that a small proportion of the mice (feral and laboratory) were positive for antibody in the majority of the colonies tested, and they speculated that few, if any, conventional mouse colonies might be entirely free of the virus; on the other hand, SPF and germ-free colonies were free of the infection. Parker et al. (1966) used the HAI test to conduct an extensive serologic survey of laboratory mouse colonies and found that only 1 of 34 colonies tested had antibody, and in this colony approximately 35% of the mice were seropositive. In a controlled study, HAI and CF seroconverters showed good correlation 1 month after inoculation; however, CF antibody titers were severalfold higher than HAI titers (J. C. Parker, 1979 unpublished observations). Comparative HAI and CF tests on 19 mouse sera from three infected colonies showed that the CF test was more sensitive, titers usually being severalfold higher than HAI titers, and it is noteworthy that 7 of the 18 CF-positive sera were HAI-negative (J. C. Parker, 1979, unpublished observations). Thus, undetected latent infections may be accounted for by the use of the less sensitive HAI test (Kraus, et al., 1968; Gleiser and Heck, 1972).

In other serologic surveys using the HAI test, Poiley (1970) did not detect K virus HAI antibody during a 1 1/2-year study which tested 2400 mice produced in six NIH Genetic Production Centers. In Canada, however, Descoteaux et al. (1977) detected K virus HAI antibody at prevalence rates of 15–60% with mean antibody titers ranging from 1:13 to 1:21 in four of five colonies examined. The findings of Descoteaux et al. (1977) in Canada are in marked contrast to those of comparable studies in the United States, where the results of serologic surveys using the HAI tests have shown that K virus infection is either rare or absent in colony-reared mice (Parker et al., 1965, 1966; Tennant et al., 1966; Van Hoosier et al., 1966; Poiley, 1970; J. C. Parker, 1979 unpublished observations). On the contrary, the prevalence data obtained by Rowe et al. (1962), using the CF test, would support and be consistent with an epizootiologic hypothesis that natural K virus infections in mice are prevalent and geographically widespread as latent enzootic infections in only a small proportion of mice in a given population. It is also possible that the CF test may detect some nonspecific or cross-reactive antibody and that the HAI test is the more accurate measure of infection (Tennant et al., 1966); however, current data would not seem to support this theory.

3 Natural History and Transmission

Beyond the observations on experimental transmission, little is known about this aspect of the natural biology of K virus. Virus has been demonstrated in lactating mammary glands from C3H mice (Kilham, 1952), lung, liver, spleen, kidney and, to a lesser extent, in brain, saliva, intestinal content, blood, and urine (Kilham and Murphy, 1953; Rowe et al., 1962; Greenlee, 1979). Blackmore et al. (undated) have stated that the virus is spread via the nasal or oral routes but cite no specific reference. On the basis of the known presence of the virus in the kidneys and urine, urine aerosols would seem to be one of the possible methods of spread, as would feces. Since the virus is stable outside the host, contaminated food, bedding, soil, or water would remain infectious for long periods, enabling the virus to remain viable and thus persist at low infectious levels in a mouse population. The possibility that insect vectors and ectoparasites could play a role should not be overlooked since the virus is present in the blood. Experimental infection of older resistant mice results in carriers (Kilham, 1952), and indeed, the first isolations of K virus were made from inapparent carriers. Thus, even though mortality is limited to very young animals, transmission among older animals might be more important in natural maintenance of colony infections since the urine and feces may remain infective for 4 weeks or more when adults are infected (Holt, 1959; Kilham, 1952). It is noteworthy that the natural pattern of infection is enzootic. Epizootics of K virus have not been reported.

Greenlee (1979) states that the natural routes of papovavirus infections in animals remain unknown, and he concluded from his study that since the liver and lung invariably demonstrated viral antigen simultaneously, these organs might well be involved secondarily by the hematogenous route. Furthermore, K virus does not appear to infect the upper or lower respiratory tract epithelium; hence these cells can hardly be the primary site. Since oral infection is more lethal than intranasal infection and is accompanied by the early appearance of viral antigen in the intestinal villi, the oral route is a strong possibility for natural transmission. It is equally possible that the jejunal endothelium is the target organ in natural infection. It should also be mentioned that given the crude state of intranasal inoculations in mice, it can be assumed that a reasonable portion of such inoculae will either be swallowed directly or coughed up and swallowed. Thus, the intranasal route would merely serve as a means of diluting an oral inoculation where the respiratory tract epithelium is not the target organ. Even less well understood at present is the observation by Greenlee (1979) that K virus replicates in the brains of neonates without apparent pathologic or behavioral consequences. It is not yet known whether replication also occurs in the brain of asymptomatically infected older mice, or what the possible late effects of brain infection might be.

Within naturally infected mouse colonies, recovered mothers confer passive immunity on their litters via maternal antibody, and because of the early development of age resistance to lethal infection, newborn mortality is rare. After weaning, any mice becoming infected would experience a subclinical and probably prolonged chronic infection in which small amounts of virus would be voided via the urine, feces, and perhaps saliva over several weeks (Rowe et al., 1962; Holt, 1959; Kilham and Murphy, 1953). The cycle would be complete when immune female virus carriers give birth to passively immunized newborn mice and simultaneously infect them via their virus-containing milk (Kilham, 1952), saliva, urine, or feces. This infection model might suggest that infection would therefore occur in mice of various ages within an infected colony. This pattern of infection was observed by Kilham and Murphy (1953) when they isolated K virus from three nursing C3H mice 6 months of age, by Kraus et al. (1968) when virus was isolated from adult mice, and by Parker et al. (1966) in a seroepizootiologic study of K virus infection in a mouse breeder colony. Holt (1959) and Derrick and Pope (1960) made similar observations. Parker et al. (1966) monitored a colony for HAI antibody over a period of 1 1/2 years. Mice 4–5 months of age seldom had HAI antibody, whereas mice 7 months of age and older were positive. Virus was not isolated from 1- to 2-month-old mice but was isolated from 4- to 5-month-old and 16-month-old mice, suggesting that the mice became infected at 4–5 months of age and subsequently seroconverted. Isolation from 16-month-old mice suggests a delayed focal infection or possibly a chronic infection lasting up to 1 year (Parker et al., 1966). It is noteworthy that the three wild mice from which Holt (1959) isolated K virus were positive for neutralizing antibody.

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Sialic Acids, Part I: Historical Background and Development, and Chemical Synthesis

Roland Schauer, Johannis P. Kamerling, in Advances in Carbohydrate Chemistry and Biochemistry, 2018

12.5.1 Plant and Other Lectins, and Virus Hemagglutinins

Lectins were first found almost exclusively in plants.398,1084–1086 Since they were detected by the agglutination of erythrocytes, they were named “hemagglutinins” or “phytohemagglutinins.” As plant lectins are able to distinguish between erythrocytes of different blood types, as early as 1954 Boyd and Shapleigh coined the name “lectin,” from the Latin legere, “to select.”1087 This definition was later used for all carbohydrate-binding proteins, irrespective of their occurrence.

To go back in history, before 1860, S. Weir Mitchell in Pennsylvania had observed agglutination of pigeon blood by the venom of a rattlesnake.1088 The first lectin, called “ricin,” was discovered in 1888 in the beans of the castor tree (Ricinus communis) by Hermann Stillmark at the University of Dorpat (now Tartu) in Estonia.1089 In fact, it was a mixture of weakly agglutinating protein toxins, which were later found to bind to galactose and N-acetylgalactosamine.1084,1090 Furthermore, Simon Flexner and Hideyo Noguchi,1091 from the Rockefeller Institute (New York, USA), described in 1902 snake venom agglutinins in some detail in the horseshoe crab (L. polyphemus)1078 and the American lobster Homarus americanus. In the first decade of the 20th century also the first bacterial agglutinins were found, which were later identified as lectins. Investigations on blood type-specific lectins stem from the early 1950s, when it was demonstrated for the first time that lectins can bind monosaccharides.1092

The already described studies of Hirst in the 1940s on the agglutination of human erythrocytes by influenza virus (see Sections 2.1 and 11.7) can be considered as the first example of the involvement of a lectin/hemagglutinin, a sialic acid-binding agent. Influenza virus hemagglutination was found to be inhibited by a brain lipid fraction, known to contain gangliosides.1093 In the following decades the structure and pathophysiological significance of the viral hemagglutinin (designated “H” antigen) was most intensively studied, until today, by the group of Hans-Dieter Klenk at Philipps-Universität Marburg (Germany).958,959,1094 Influenza viruses demonstrate pronounced receptor binding specificity. Human influenza viruses preferentially bind to Neu5Ac(α2→6)Gal sequences, whereas avian influenza viruses prefer Neu5Ac(α2→3)Gal as ligand (or receptor in the terminology of virologists).1095 Competitive inhibitors of the binding of avian or human influenza viruses to sialylated glycans are soluble glycoconjugates carrying (α2→3)- or (α2→6)-linked sialic acids, respectively. The earlier discussed mucin from the nests of the Chinese swiftlet, genus Aerodramus collocalia (collocalia mucoid, edible bird's nest substance),1096 rich in sialic acids, is a potent inhibitor of the agglutination of myxoviruses.1097 This may have been the reason that it has been used in Chinese medicine for hundreds of years in order to prevent and cure influenza and its following bronchial diseases. The substance, which is a good substrate for sialidase, has additional health benefits and is therefore highly esteemed in Asia.1098

The best known sialic acid-recognizing plant lectins are WGA, accepting Neu5Ac and (β1→4)-linked GlcNAc residues, S. nigra agglutinin (SNA) from the bark of the elderberry bush, recognizing (α2→6)-linked sialic acid to galactose, and M. amurensis lectin (MAA), specific for (α2→3)-linked sialic acid to galactose.1084 The fractions of these plant lectins are believed to protect the plants from pathogenic microorganisms and fungi, as well as from herbivorous animals. It was found that the bark lectin SNA provoked toxic effects in animals and created a reaction of avoidance (Fig. 35).1099 One of the authors (R.S.) observed that during a very cold winter with much snow, mammals, mainly rabbits, fed on the bark of various bushes, but not on that of the elderberry bush. Both SNA and MAA are used regularly in structural analysis protocols, i.e., lectin affinity chromatography, histochemistry, or lectin microarrays.275

Virus Hemagglutination - an overview (2)

Fig. 35. Lectins, for example, the sialic acid-binding Sambucus nigra agglutinin (SNA), protect plants against herbivorous and chewing animals.

Reproduced from Peumans, W. J.; Van Damme, E. J. M. Lectins as Plant Defense Proteins. Plant Physiol. 1995, 109, 347–352. Copyright American Society of Plant Biologists.

Sialic acid-recognizing proteins are manifold in Nature. The first sialic acid-binding protein from vertebrates reported was Complement Factor H, an early response factor of the innate immune system.1100,1101 In a thorough search about 230 sialic acid-specific lectins in viruses (being the largest group), bacteria, toxins, protozoa, fungi, plants, invertebrates, and vertebrates were described.1102 In the intervening time, more sialic acid receptors have been detected, especially in the field of virus research, e.g., of the human Noro virus,1103 the Middle East Respiratory Syndrome Coronavirus (MERS-CoV),1104 and the Infectious Salmon Anemia Virus (ISAV), the latter binding to Neu4,5Ac2.1105 Most of these sialic acid lectins bind to Neu5Ac, but a few only to Neu5Gc or to both sialic acid types. An example of Neu5Gc as virus receptor is the transmissible porcine gastroenteritis coronavirus.1106 The various lectins may discriminate between (α2→3) and (α2→6) linkages and rarely prefer (α2→8) linkages, like e.g., siglec-7 and -11. Some invertebrate and viral lectins bind to 4- or 9-O-acetylated sialic acids, the best known example being influenza C virus.826,1102

Not much is known about how and where influenza C viruses enter the human organism, but the human respiratory tract is the most likely place. In the nasal secreted mucin of only one person studied so far, about 10% of the sialic acids were 9-O-acetylated. In a pool of nasal mucosa probes collected after surgery in 1994, a 9-O-acetylated sialoglycoprotein fraction of 100–130kDa was detected by Western Blot analysis. This could be the influenza C virus receptor. Since also the ganglioside fraction was found to be O-acetylated, the influenza C virus receptor must be studied further.1107 Influenza C virus hemagglutinins, specific for (α2→3) and (α2→6) linkages, can differentiate between receptor determinants bearing N-acetyl-, N-glycolyl-, and O-acetylated sialic acids. This was shown by the agglutination of Neu5Ac, Neu5Gc, or Neu5,9Ac2 covering erythrocytes.1108

Very recently, probes from viral sialic acid-binding proteins were developed to detect 4-O-acetyl, 9-O-acetyl, and 7,9-di-O-acetyl sialic acids on cells and tissues of humans and a great variety of animals.407 It is astonishing how widely distributed these esterified sialic acids are. The HE proteins were expressed in insect cells and fused to the Fc region of human IgG1 and to a hexahistidine sequence for histochemical or microarray use (see also Section 7.4). Binding of influenza A virus and Siglec-2 (CD22) is inhibited by Neu5Ac O-acetylation.826

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Symposium-in-Print: Chemistry and Biology of Natural Products

Howard C. Hang, Carolyn R. Bertozzi, in Bioorganic & Medicinal Chemistry, 2005

In the early 1900s, two related discoveries on the “agglutination” of erythrocytes invigorated research on mucins. The first was the seminal discovery of the ABO blood groups in human serum by Karl Landsteiner in 190110 and the second was the characterization of influenza virus hemagglutination in 1942 by Hirst and Burnet.11 In particular, the molecular basis for ABO blood group specificity sparked the structural analysis of erythrocyte extracts by the Morgan and Watkins and Kabat laboratories.12 These landmark studies revealed the structures of the oligosaccharide antigens (A, GalNAcα1-3(Fucα1-2)Galβ1-4(3)GlcNAc; B, Galα1-3(Fucα1-2)Galβ1-4(3)GlcNAc; and O(H), Fucα1-2Galβ1-4(3)GlcNAc) that governed the ABO blood group specificities and also demonstrated these glycans were attached to mucin scaffolds through GalNAc residues. However, the alkaline conditions used to liberate the O-linked glycans from the proteins precluded the characterization of the glycopeptide linkage. The α-GalNAc linkage to Thr/Ser was ultimately determined by Weissman and Hinrichsen in 1969 with a purified α-N-acetylgalactosaminidase from bovine liver.13

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What is the viral hemagglutination? ›

Hemagglutination is a reaction that causes clumping of red blood cells in presence of some enveloped viruses, such as the influenza virus.

Which viruses are detected by haemagglutination test? ›

The haemagglutination test is used to quantify the amount of Newcastle disease virus in a suspension. This is done by carrying out two-fold serial dilutions of the viral suspension in a microwell plate and then testing to determine an end point.

Which viruses cause hemagglutination? ›

Hemagglutinating encephalomyelitis virus (HEV), unlike other Coronaviruses, readily agglutinates a variety of red blood cells.

What is the principle of hi test? ›

The hemagglutination inhibition (HI) assay is used to titrate the antibody response to a viral infection. The HI assay takes advantage of some viruses' ability to hemagglutinate (bind) red blood cells, therefore forming a “lattice” and preventing the red blood cells from clumping.

Why do viruses cause hemagglutination? ›

Scientists use a test called the hemagglutination inhibition assay (HI test) to antigenically characterize influenza viruses. HA proteins on the surface of influenza viruses can bind to red blood cells and “glue” them together, forming a lattice structure (this is known as “hemagglutination”).

How does hemagglutination work? ›

Blood agglutination or hemagglutination is a type of agglutination that occurs when antibodies bind to specific binding sites on antigens expressed on red blood cells (RBCs). Because of the ease of a clumping reaction, hemagglutination is a critical technique in blood type classification.

What part of virus contains hemagglutinin? ›

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

What are the stages of hemagglutination? ›

The antigen-antibody reactions that are used most in blood banking are known as hemagglutination, i.e., they cause the agglutination of red cells. These reactions take part in two stages, sensitization and agglutination.

What are the factors affecting hemagglutination? ›

Some of the factors that are known to affect the agglutination of various erythrocytes by viruses are the age of the donor animal, the hydrogen ion concentration of the diluent and the temperatures at which erythrocytes are allowed to sediment.

What does hemagglutinin mean? ›

Listen to pronunciation. (HEE-muh-GLOO-tih-nin-NOOR-uh-MIH-nih-days) A protein found in the outer coat of paramyxoviruses. This protein helps virus particles bind to cells, making infection easier.

What is the meaning of hemagglutinin? ›

haemagglutinin in British English

or US hemagglutinin (ˌhiːməˈɡluːtɪnɪn , ˌhɛm- ) noun. an antibody that causes the clumping of red blood cells.

What are the 4 h viruses? ›

Not to downplay how dangerous STDs can be, but the “4 H's” are the sexually transmitted diseases that typically warrant the most fear and dread. The Four H's are all viral STDs: Herpes, Human papillomavirus (HPV), Human Immunodeficiency Virus (HIV), and Hepatitis C.

Why do we do HI test? ›

The hemagglutination inhibition (HI) assay for influenza A virus has been used since the 1940s. The assay may be utilized to detect or quantify antibodies to influenza A viruses and can be used to characterize differences in antigenic reactivity between influenza isolates.

What is a hemagglutination inhibition test used for? ›

Hemagglutination-inhibition (HI) assay is a classical laboratory procedure for the classification or subtyping of hemagglutinating viruses. For influenza virus, HI assay is used to identify the hemagglutinin (HA) subtype of an unknown isolate or the HA subtype specificity of antibodies to influenza virus.

Why 4ha is used in hi test? ›

4. HA Assay. NOTE: To ensure that the HI assays are comparable between several plates, the same amount of virus particles must be used for each plate. The HA assay (also called HA titration) is performed to quantify the virus particles necessary for hemagglutination, and is recorded in HA units.

What does hemagglutinin interact with? ›

Hemagglutinin-neuraminidase (HN) protein, which is responsible for virus attachment, interacts with the fusion protein in a virus type-specific manner to induce efficient membrane fusion.

What is the difference between agglutination and hemagglutination? ›

Agglutination is a process where red blood cells are not involved in clumping, while hemagglutination is a process where blood red blood cells are involved in clumping. This is the key difference between agglutination and hemagglutination.

Is hemagglutinin a virus receptor? ›

Important contributions to our understanding of influenza infections have come from the studies on hemagglutinin (HA), a viral coat glycoprotein that binds to specific sialylated glycan receptors in the respiratory tract, allowing the virus to enter the cell (3–6).

What are the basic principles of hemagglutination reaction? ›

7.7 Hemagglutination

The main principle of HA is based on the characteristics of pathogens' surface envelope proteins that are able to agglutinate to human or animal red blood cells and bind to its N-acetylneuraminic acid. This process is very commonly used in characterization of influenza viruses.

What is the structure of hemagglutinin? ›

Hemagglutinin consists of a globular head and a stem. The globular head consists of three chains, Chains A, C, and E. The stem of the protein consists of three chains as well, Chains B, D, and F.

Where does hemagglutinin attach? ›

The viral hemagglutinin attaches to host cells via sialic acid containing receptors. Viral replication occurs in both upper and lower respiratory tracts.

What is the effect of hemagglutinins? ›


Hemagglutinins are characterized and detected by their action on red blood cell membranes, causing the blood cells to clump together. Other cells can also be affected. The receptor site on the cell surface must be exposed in order to react with a specific lectin.

What type of protein is hemagglutinin? ›

Hemagglutinin (HA) or Haemagglutinin (BE) is an antigenic glycoprotein found on the surface of the influenza viruses. It is responsible for binding the virus to the cell that is being infected.

Is hemagglutinin harmful? ›

Hemagglutinin in Action

Hemagglutinin is a deadly molecular machine that targets and attacks cells.

What type of agglutination is 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.

What are the benefits of hemagglutinin? ›

Viral hemagglutinin stimulates the production of antibodies by the host's immune system. These antibodies bind to a portion of the hemagglutinin antigen known as an epitope, thereby tagging the virus for immune destruction.

Is hemagglutinin a gene? ›

The complete sequence of a hemagglutinin (HA) gene of a recent human influenza A strain, A/Victoria/3/75, is 1768 nucleotides long and contains the information for 567 amino acids.

What are the 3 main groups of viruses? ›

Based on their host, viruses can be classified into three types, namely, animal viruses, plant viruses, and bacteriophages.

What STDs Cannot be cured? ›

Eight pathogens are linked to the greatest incidence of STIs. Of these, 4 are currently curable: syphilis, gonorrhoea, chlamydia and trichomoniasis. The other 4 are incurable viral infections: hepatitis B, herpes simplex virus (HSV), HIV and human papillomavirus (HPV).

What is the meaning of hi positive? ›

Refers to a person who is infected with the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immunodeficiency syndrome (AIDS).

What are the disadvantages of Haemagglutination? ›

Disadvantages: 1) Sensitivity is low. 2) Not all viruses contain hemagglutinins.

What is the difference between HA and hi test? ›

HI is closely related to the HA assay, but includes anti-viral antibodies as “inhibitors” to interfere with the virus-RBC interaction. The goal is to characterize the concentration of antibodies in the antiserum or other samples containing antibodies.

Why is agglutination test important? ›

Agglutination tests are frequently used for initial confirmation of specific pathogens. Since antibodies to the target organism may cross-react with other organisms and autoagglutination may occur, these must be considered as screening tests and further confirmation will usually be necessary.

How do you calculate 4 HA unit? ›

Calculation of 4HA units: 4HAU is obtained by dividing 1HAU with four. If 1HAU is 512; then 4HAU is 512/4 = 128. The virus should be diluted to 1:128 before proceeding with HI test.

When would a hemagglutination titer be used? ›

Hemagglutination is used for the diagnosis of some enveloped viruses such as influenza viruses. This method relies on the specific feature of some enveloped viruses that can adsorb to red blood cells (RBCs).

What is viral Hemadsorption? ›

Hemadsorption occurs when erythrocytes added to a myxovirus-infected tissue culture are adsorbed to the host-cell surface. The erythro- cytes combine with virus-specific material at the cell surface, since the reaction can be prevented by prior treatment of the tissue culture with im- mune serum.

Where is hemagglutinin located in a virus? ›

Hemagglutinin (HA) or Haemagglutinin (BE) is an antigenic glycoprotein found on the surface of the influenza viruses. It is responsible for binding the virus to the cell that is being infected.

What viruses cause hemadsorption? ›

For some viruses, such as influenza or parainfluenza viruses, cellular changes may not be evident. To detect the presence of these viruses, the hemadsorption test is commonly used. Influenza and parainfluenza viruses express a viral hemagglutinin on the surface of infected cells.

What causes hemadsorption? ›

The phenomenon of hemadsorption is dependent upon selective attachment of erythrocytes onto the monolayer surface of tissue culture cells. It is demonstrated by addition of erythrocytes to a tissue culture system in which propagation of a hemagglutinin-producing virus has occurred.

What is the purpose of hemadsorption? ›

Hemadsorption can be used to demonstrate infection with noncytopathogenic as well as cytocidal viruses, and can be demonstrated very early, e.g., after 24 hours, when only a small number of cells in the culture are infected.

What is the effect of hemagglutinin? ›


Hemagglutinins are characterized and detected by their action on red blood cell membranes, causing the blood cells to clump together. Other cells can also be affected. The receptor site on the cell surface must be exposed in order to react with a specific lectin.

What is hemagglutinin made of? ›

Hemagglutinin consists of a globular head and a stem. The globular head consists of three chains, Chains A, C, and E. The stem of the protein consists of three chains as well, Chains B, D, and F.

Is hemagglutinin an antibody? ›

Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. Plays a major role in the determination of host range restriction and virulence.


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