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At least 19 recordsLinked to original sources
PubMed1977

The effects of neuraminidase on concanavalin A agglutination of erythrocytes: evidence for adsorption of neuraminidase to erythrocyte membrane.

Neuraminidase-treated human erythrocytes, but not untreated erythrocytes, were agglutinated by concanavalin A. The degree of concanavalin A agglutinability was not directly related to sialic acid removal by neuraminidase. While maximal sialic acid release was obtained with 5 units neuraminidase/2 x10(9) erythrocytes, maximal concanavalin A agglutination was only obtained after exposure to 20 units neuramindase. Binding of 3H-concanavalin A by erythrocytes was 10-fold higher with rabbit compared to human red cells. Neuraminidase treatment of human erythrocytes caused a relative increase in 3H-concanavalin binding, but the absolute amount was still 10-fold less than that bound to rabbit erythrocytes. Specific adherence of neuraminidase to Con A-Agarose could not be demonstrated. There was no evidence for contamination of the neuraminidase preparation with proteases using a sensitive assay. These studies suggest that neuraminidase absorbs to erythrocytes by a mechanism other than removal of sialic acid.

Adsorption↗
PubMed1976

Comparative efficacy of neuraminidase-specific and conventional influenza virus vaccines in induction of antibody to neuraminidase in humans.

Groups of college students received either conventional A/England/42/72 (H3N2) vaccine (X-37), an antigenic hybrid (Heq1N2) vaccine (X-38) containing the same neuraminidase (and thus effectively neuraminidase-monospecific), or a placebo injection. The vaccines contained 798 and 643 chick cell-agglutinating units per dose, respectively, and equivalent immunogenic units of N2 as defined in antigenic extinction tests in rabbits. All subjects had antibody to N2 before immunization, and mean initial titers were comparable in both vaccine groups. Homotypic hemagglutination-inhibition response to vaccine hemagglutinin was slightly more frequent (77%) but of lower magnitude in the students vaccinated with X-38 than in those vaccinated with X-37. Significant antibody response to N2 was observed in 25% of those vaccinated with X-37 and in 69% of those vaccinated with X-38. Mean antibody response to N2 was twofold greater in those vaccinated with X-38. Heterotypic hemagglutination-inhibition was seen in 56% of those receiving X-38 vaccine. In preliminary plaque-inhibition titrations this heterotypic antibody did not have neuralizing activity. Testing of antibody response to N2 with earlier neuraminidase antigens demonstrated "original antigenic sin" from earlier priming. The superiority of the "neuraminidase-specific" X-38 (Heq1N2) vaccine as an immunogen for antibody to neuraminidase may reflect different processing of N2 when it is associated with a hemagglutinin to which the study population has not been previously exposed.

Adult↗
PubMed1977

Neuraminidase content of influenza vaccines and neuraminidase antibody responses after vaccination of immunologically primed and unprimed populations.

Vaccines prepared with influenza A/swine/1976/37-like virus contained neuraminidase activity comparable to that of H3N2 vaccines, whereas little neuraminidase activity could be detected in influenza A/New Jersey/76 vaccines. In single-dose vaccine studies, A/swine/1976/37-like split-virus vaccine induced antibody to neuraminidase (NAAb) in about 20% of children younger than 18 years and this NAAb response was better than or equal to the antibody response to the vaccine's hemagglutinin (HAAb). In immunologically primed adults, the NAAb response to a single dose of Hsw1N1 or H3N2 vaccine was 38%-54%, but this value was about 1.7-fold lower than that for HAAb response. Children six to 17 years old given two doses of A/swine/1976/37-like vaccine had an overall 70% NAAb response, whereas children of similar age had an overall 30%-48% NAAb response to two doses of A/Victoria/3/75 (H3N2) virus. The findings support a hypothesis that the NAAb response to influenza vaccines can be suppressed if subjects receiving the vaccine are immunologically primed to its hemagglutinin component. NAAb responses in the absence of HAAb responses occur in only about 5% of vaccinated persons who are immunologically primed to both the hemagllutinin and neuraminidase of the vaccine.

Adolescent↗
PubMed1975

Membrane-bound neuraminidases of rat liver. Neuraminidase activity in Golgi apparatus.

The bulk (60 to 65%) of the neuraminidase activity present in rat liver homogenates was found in the M + L (mitochondria plus lysosomes) fraction, The patterns of subcellular distribution were essentially identical whether disialogangliosides or neuramin-lactose (2 yields 3') were utilized as substrates. A new neuraminidase, which hydrolyzes sialyl trisaccharides but which does not act upon glycoproteins and gangliosides, was detected in Golgi apparatus. Unlike the other particulate neuraminidases of rat liver, the Golgi enzyme is stimulated by prior incubation and by the addition of Ca2+ or Zn2+ at 1 mM concentration. Although plasma membrane-rich fractions are often contaminated by Golgi membranes the marked differences in their enzymic properties allowed a clear distinction between the neuraminidases present in these two types of membranes.

Animals↗
PubMed1979

Adaptation of the influenza neuraminidase and neuraminidase-inhibition assays to the microtitrator system.

A micro-method based on Warren's colour reaction has been developed for influenza neuraminidase and neuraminidase-inhibition assays. Extraction with butanol is omitted and the assay is performed in wells of special plexiglass trays, where the reaction mixon and compared to controls in the same tray. The micro-assay, being inexpensive, time-saving and easy to perform even in poorly equipped laboratories, is suitable for large-scale serological screening and identification of the neuraminidase antigen of isolates.

Antibodies, Viral↗
PubMed1975

The production of neuraminidase by food poisoning strains of Clostridium welchii (C. perfringens).

The production of neuraminidase by a classical strain of Clostridium welchii (C. perfringens) type A was studied. Good yields were produced in 5% Proteose Peptone-water medium (PPW5); the enzyme was essentially extracellular but some further neuraminidase could be released by ultrasonic disintegration of the cells. This also released N-acyl neuraminic acid-aldolase (NAN-aldolase) and the degree to which this interferes with the assay for neuraminidase was evaluated. Forty-one British reference food-poisoning strains of C. welchii type A were examined for extracellular neuraminidase production in PPW5. Twelve of 17 strains that produce so-called heat-sensitive spores were neuraminidase positive whereas 20 of 24 strains that are non-haemolytic and produce very heat-resistant sporeswere neuraminidase negative. Variation was found in the ability to produce neuraminidase among strains of a single Hobbs' serotype; four Hobbs' type-13 strains produced neuraminidase but a fifth did not. Disruption of the cells of a Hobbs' type-2 strain that did not produce any extracellular neuraminidase released NAN-aldolase but there was no evidence of cell-associated neuraminidase. British food-poisoning strains of C. welchii type A thus include some that are clearly neuraminidase positive and some that still cannot be shown to produce neuraminidase. There is no correlation between lack of neuraminidase production and the ability to cause food poisoning, although the majority of non-haemolytic heat-resistant strains do not produce neuraminidase. It remains possible that neuraminidase may play a part in C. welchii gas gangrene; it is suggested that the ability to define neuraminidase-negative strains may now be of value in investigating this possibility.

Clostridium perfringens↗
PubMed1979

Enzymatic properties of neuraminidases from Arthrobacter ureafaciens.

Neuraminidase I and neuraminidase II from Arthrobacter ureafaciens were characterized. As determined by gel filtration on Ultrogel AcA 44, the molecular weights of neuraminidases I and II were 51,000 and 39,000, respectively. Neuraminidases I and II were similar to each other in their enzymatic properties except for the substrate specificities towards gangliosides and erythrocyte stroma. Their optimal pHs were between 5.0 and 5.5 with N-acetylneuraminosyl-lactose or bovine submaxillary mucin as substrates, but with colominic acid as a substrate, the pH optimum was between 4.3 and 4.5. They were most active around 53 degrees C, were stable between pH 6.0 and 9.0, and were thermostable up to 50 degrees C. They did not require Ca2+ for activity and were not inhibited by EDTA. They were inhibited only slightly or not at all by p-chloromercuribenzoic acid of Hg2+. Both neuraminidases I and II were able to hydrolyze the alpha-ketosidic linkage of N-glycolylneuraminic acid as well as that of N-acetylneuraminic acid, and were able to liberate substantially all of the sialic acid from various kinds of substrates. However, they cleaved only about 50% of the sialic acid from bovine submaxillary mucin. The saponification of bovine submaxillary mucin by mild alkali treatment, on the other hand, resulted in an increased susceptibility to the neuraminidases and brought about the complete liberation of sialic acid. Remarkable differences were observed between neuraminidases I and II as regards substrate specificities on gangliosides; the initial rate of hydrolysis by neuraminidase I was 74 times, and its maximum velocity constant was 91 times those of neuraminidase II. The addition of sodium cholate markedly stimulated the enzymatic hydrolysis of gangliosides, and increased the maximum velocity constant of neuraminidase I twofold and that of neuraminidase II 143-fold. Although neuraminidases I and II were able to hydrolyze (alpha,2-3), (alpha,2-6), and (alpha,2-8) linkages, the initial rate of hydrolysis of N-acetylneuraminosyl-alpha,2-6-lactose was greater than that of the alpha,2-3-isomer.

Arthrobacter↗
PubMedDate not supplied

[Strain differences in the neuraminidase specificity of subtype N 1].

Nine strains having neuraminidase of subtype N1 and two strains in which the appurtenance of neuraminidase to subtype N1 was determined in the course of the study were examined for the antigenic specificity of the functional center of the enzyme in the cross neuraminidase activity inhibition test. Neuraminidase of the strains A/Swine/Tatarstan/64 and A/Swine/Ikshurminsk was shown to belong to the subtype N1 but to differ from neuraminidase of the strain A/Swine/Iowa/15/30. Neuraminidase of the strain A/Chicken/USSR/314/67 differs from neuraminidases of A/PR8/34, A/WS/33, and A/Swine/Iowa/15/30 but is related to neuraminidases of the strains A/New Jersey/8/76, A/duck/Germany/1868/68 and A/Chicken/Scotland/59. The A/New Jersey/8/76 neuraminidase is not related to neuraminidases of the strains A/PR8/34 and A/WS/33 but is related to neuraminidases of strains isolated from swine and domestic fowl. The disclosed considerable strain variations in the antigenic specificity of neuraminidases attest to heterogeneity of the subtype N1 and the possibility of its subdivision into groups.

Antigens, Viral↗
PubMed1978

Neuraminidase production by clostridia.

The production of neuraminidase (EC 3.2.1.18) by a range of clostridial species was investigated with techniques previously developed to distinguish neuraminidase-negative and neuraminidase-positive strains of Clostridium perfringens (welchii). Large amounts of extracellular neuraminidase were produced by representative strains of C. perfringens and C. septicum in the test media. Under similar conditions, two strains each of C. chauvoei and C. tertium were found to produce small amounts of the enzyme. All of 12 strains of C. sordellii were clearly shown to produce neuraminidase, often in large amounts, but none of five strains of the closely related but non-pathogenic C. bifermentans had demonstrable neuraminidase activity. No neuraminidase was produced by C. novyi (oedematiens) types A-D (10 strains), C. tetani (6), C. botulinum types A, B, C or E (4), C. sporogenes (4), C. histolyticum (4) or by single strains of five other clostridial species. Clostridial neuraminidase was predominantly extracellular and was not calcium-dependent. The investigation took account of variations in growth and enzyme production in different media. It was necessary to prolong the neuraminidase-assay reaction time to 24 h and to monitor for the presence of NAN-aldolase (EC 4.1.3.3) to define true negatives. It is suggested that neuraminidase production may be of value in taxonomic studies and that its production by several pathogenic species of clostridia may be of interest in studies of pathogenicity and virulence.

Calcium↗
PubMed1977

Neuraminidase and tumor immunotherapy.

Preliminary results of first clinical studies with the enzyme neuraminidase call attention to a new kind of cancer treatment. This promising approach to tumor immunotherapy was entered into the clinical phase as a consequence of successful experimental studies in tumor-bearing mice, rats and dogs. In this review, the presently known and essential results of experimental and clinical studies on tumor immunotherapy by means of neuraminidase are presented as well as some necessary and critical considerations in this context. Moreover, out of a broad variety of results of biochemical and biological in vitro studies, it was attempted to select the more essential knowledge which could contribute to a better understanding of the still rather unclear in vivo mode of action of the enzyme neuraminidase. In a first brief paragraph (1.0), the biochemically characteristic data of the enzyme neuraminidase is presented. In the second section (2.0), the basic knowledge about the effects of neuraminidase on cell behavior is rather amply contained. Here, on the one hand, the biophysical and biochemical alterations are mentioned, the so-called ""unmasking'' effects are reconsidered and, on the other hand, the effects on the immunologically responding cell are discussed. In a third section (3.0), the diverse findings from animal experiments using neuraminidase-treated tumor cells are confronted, whereby tumor transplantation experiments and tumor therapy experiments are dealt with separately. The last section (4.0) reports about the first clinical studies with neuraminidase-treated autologous as well as homologous tumor cells, which partly brought about rather surprising and astonishing success. On the basis of recent findings by the study group of the authors, the more prior and sometimes discrepant results of various groups are critically considered. The problems of alteration of antigenicity and of other properties of cells through splitting off membrane-bound neuraminic acid, the facts of adjuvanticity of neuraminidase itself, the relation of successful therapy to dose dependency as well as the relation of undesirable methods for tumor mass reduction to the immunological responsiveness of the tumor bearer were especially looked into.

Animals↗
PubMed1992

Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex.

The crystal structure of the complex between neuraminidase from influenza virus (subtype N9 and isolated from an avian source) and the antigen-binding fragment (Fab) of monoclonal antibody NC41 has been refined by both least-squares and simulated annealing methods to an R-factor of 0.191 using 31,846 diffraction data in the resolution range 8.0 to 2.5 A. The resulting model has a root-mean-square deviation from ideal bond-length of 0.016 A. One fourth of the tetrameric complex comprises the crystallographic model, which has 6577 non-hydrogen atoms and consists of 389 protein residues and eight carbohydrate residues in the neuraminidase, 214 residues in the Fab light chain, and 221 residues in the heavy chain. One putative Ca ion buried in the neuraminidase, and 73 water molecules, are also included. A remarkable shape complementarity exists between the interacting surfaces of the antigen and the antibody, although the packing density of atoms at the interface is somewhat looser than in the interior of a protein. Similarly, there is a high degree of chemical complementarity between the antigen and antibody, mediated by one buried salt-link, two solvated salt-links and 12 hydrogen bonds. The antibody-binding site on neuraminidase is discontinuous and comprises five chain segments and 19 residues in contact, whilst 33 neuraminidase residues in eight segments have 899 A2 of surface area buried by the interaction (to a 1.7 A probe), including two hexose units. Seventeen residues in NC41 Fab lying in five of the six complementarity determining regions (CDRs) make contact with the neuraminidase and 36 antibody residues in seven segments have 916 A2 of buried surface area. The interface is more extensive than those of the three lysozyme-Fab complexes whose crystal structures have been determined, as judged by buried surface area and numbers of contact residues. There are only small differences (less than 1.5 A) between the complexed and uncomplexed neuraminidase structures and, at this resolution and accuracy, those differences are not unequivocal. The main-chain conformations of five of the CDRs follow the predicted canonical structures. The interface between the variable domains of the light and heavy chains is not as extensive as in other Fabs, due to less CDR-CDR interaction in NC41. The first CDR on the NC41 Fab light chain is positioned so that it could sterically hinder the approach of small as well as large substrates to the neuraminidase active-site pocket, suggesting a possible mechanism for the observed inhibition of enzyme activity by the antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1977

Influenza A neuraminidase antibodies in children and young adults studied by serum absorption.

A study is described of influenza A anti-neuraminidase antibodies in the sera of young people of three different groups. Each serum was individually absorbed with viruses containing the N2 neuraminidases of 1957, 1968 and 1972. Rabbit antisera prepared against the viruses were similarly absorbed. Results obtained with the animal sera suggested that these neuraminidases were antigenically distinct, but the human sera had a broader range of anti-neuraminidase activity and gave indication of asymmetric antigenic relationships. Earlier workers who surveyed anti-haemagglutinin antibodies reported that the virus of primary infection absorbed all antibodies, and the virus of secondary infection only those directed against itself. We too found that the virus of secondary infection absorbed only homologous anti-neuraminidase antibody. However, although the primary infecting virus did absorb some secondary antibody, this absorption was incomplete and it lessened with the lengthening of the time interval between the primary and secondary infecting viruses. A similar pattern was seen with anti-haemagglutinin antibodies. Absorption of anti-neuraminidase antibodies from human sera proved much more difficult than absorption of anti-haemagglutinin antibodies particularly after repeated influenza virus infections. The relative rarity of antigenic shift in the neuraminidase subunit also creates problems in the interpretation of results of serum neuraminidase antibody surveys.

Adult↗
PubMed1979

Neuraminidase-dependent hamagglutination of human erythrocytes by human strains of Actinomyces viscosus and Actinomyces naeslundii.

Human A, B, and O erythrocytes (RBC) were agglutinated by many human strains of Actinomyces viscosus and A. naeslundii. At 37 degrees C, these bacterium-mediated hemagglutination reactions required the action of bacterial neuraminidase upon the RBC; however, at 4 degrees C, the requirement for neuraminidase was not as striking. Bacterial cell suspensions which caused hemagglutination at 37 degrees C contained both soluble extracellular and cell-associated neuraminidase activities as shown by enzyme assays using a soluble substrate (i.e., alpha 1-acid glycoprotein). Bacterium-mediated hemagglutination occurred only in the presence of soluble neuraminidase activity, and the rate of hemagglutination could be inhibited by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, a competitive inhibitor of purified soluble neuraminidase from A. viscosus T14V. Suspensions of bacteria which contained only cell-associated neuraminidase activity were unable to initiate hemagglutination, but they caused immediate hemagglutination when mixed with neuraminidase-treated RBC. All hemagglutination reactions were reversible in the presence of 0.02 M lactose and were abolished by heating (85 degrees C for 30 min) the actinomycete cells but not the RBC. The proposed mechanism of hemagglutination involves two sequential steps: (i) the action of neuraminidase to unmask galactose-containing receptors on the RBC and (ii) the multivalent binding of these receptors by many low-affinity lection sites on the bacterial surface.

Actinomyces↗
PubMed1975

Functional significance of neuraminidase in the replication cycle of influenza viruses.

An influenza A strain with temperature sensitive neuraminidase was used for investigation of the functional significance of neuraminidase in different stages of the replication cycle. Heat inactivation of the neuraminidase does not diminish infectivity. Therefore, neuraminidase is not necessary for adsorption, penetration, and uncoating. At temperatures which inhibited neuraminidase activity there was also a reduction of intracellular haemagglutinin production but based on observations with a recombinant strain this was considered to be the consequence of a separate ts defect. Using quantitative haemadsorption to determine virus-dependent alteration of the cellular membrane no evidence was found that neuraminidase is involved in this process. However, release of haemagglutinin was considerably reduced if neuraminidase activity was diminished by temperature elevation. This function of the enzyme in the latest stage of the replication cycle can be substituted by V. cholerae neuraminidase.

Culture Techniques↗
PubMed1975

Antigenic variation of neuraminidase of human type A influenza (H3N2) viruses isolated in Berlin (West).

After the emergence of the A/Hong Kong/1/68 (H3N2) strain of influenza virus antigenic variation of the hemagglutinin and neuraminidase antigens have been demonstrated leading to the identification of the variants A/England/42/72,a/Port Chalmers/1/73 and A/Scotland/840/74. This study describes antigenic changes of neuraminidases in influenza viruses isolated since 1968 in Berlin (West). A collection of 13 isolates of human type A influenza was studied in neuraminidase inhibition tests. The results are in line with data from other laboratories indicating a major change in the neuraminidase antigen as early as December 1969. The strains isolated at that time cross-reacted with an antiserum against the N2-Hong Kong enzyme to less than 50%. During the following years (1970 to 1972) the neuraminidase remained fairly stable. Serological cross-reactions showing 47 to 38% inhibition as compared to the homologous N2-antigen. The neuraminidase of the A/Berlin/3/72 strain revealed a close antigenic relationship to the later appearing A/Port Chalmers 1/73 variant. Two strains isolated in 1975 (January) showed an even further drift away from the then representative A/Port Chalmers/1/73 strain. The fact that the neuraminidase antigens of the Berlin viruses had changed in December 1969 may account for the severe 1969/70 influenza epidemic in Berlin affecting a large proportion of the population. Prevalent anti-neuraminidase antibodies may play a role in restricting a variant carrying a new hemagglutinin to primarily infected individuals by cross-reacting with a closely related enzyme.

Antigens, Viral↗
PubMed1978

Studies on brain cytosol neuraminidase. II. Extractability, solubility and intraneuronal distribution of the enzyme in pig brain.

The origin and properties of cytosolic neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) from pig brain were studied. 1. The brain extracts containing the cytosol derived from neuronal bodies and glial cells carry 0.69 munits neuraminidase/g fresh tissue. The behaviour of neuraminidase during extraction closely paralleled that of authentic cytosolic enzyme, lactate dehydrogenase; whereas, it differed from that of the lysosomal enzymes, beta-hexosaminidase and beta-galactosidase, also found in the extracts. 2. Nerve endings from either crude or purified preparations, when treated by hypoosmotic shock, released neuraminidase activity up to a maximum of 1.25 munits/g fresh tissue. The behaviour of releasable neuraminidase was always identical to that of lactate dehydrogenase and very similar to that of ATPase and acetylcholinesterase. Typical lysosomal enzymes, however, such as beta-galactosidase and beta-hexosaminidase, behaved differently under the same conditions. This neuraminidase activity is thought to be derived from the cytosol of nerve endings. 3. The specific activity of neuraminidase in nerve-ending cytosol is 15--20 times that in neuronal body and glial cell cytosol. Some properties (pH, Km value, V/t relationship) of the cytosolic enzymes of different origin are similar; others (stability on standing at 4 degrees C; resistance to freezing and thawing) are different. Hypoionic solutions caused both cytosolic neuraminidases to slowly precipitate and to assume a stable insoluble form which was still active.

Animals↗