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Biomedical subjects

M N Matrosovich

Publications and source records attributed to M N Matrosovich.

At least 37 records · Page 2Linked to original sources
PubMed1995

Human influenza virus recognition of sialyloligosaccharides.

Sialic acids are essential components of cell-surface receptors utilized by influenza viruses. To evaluate the recognition of asialic sugar parts of the receptor, three representative strains of human influenza A and B viruses were tested for their binding of a panel of sialyloligosaccharides. The highest affinity binding carbohydrate determinants recognized by the viruses in a context of different core structures were Neu5Ac alpha 2-3Gal for the type B virus, Neu5Ac alpha 2-6 Gal for the H3 subtype virus, and Neu5Ac alpha 2-6Gal beta 1-4GlcNAc for the H1 subtype virus. Penultimate to these determinants parts of the sialyloligosaccharides studied either contributed less significantly to the binding affinity, or interfered with the binding.

Binding Sites↗
PubMed1994

Synthetic polymeric inhibitors of influenza virus receptor-binding activity suppress virus replication.

A new approach to anti-influenza chemotherapy is based on the development of synthetic inhibitors of virus attachment to host cells. These inhibitors are prepared by anchoring the minimum receptor determinant of influenza virus, sialic acid, to polymeric or liposomal carriers. In this study, a series of poly(acrylic acid-co-acrylamides) and dextrans bearing pendant glycylamidobenzylsialoside groups were synthesized and evaluated for their binding to a panel of influenza A and B virus strains and for their ability to inhibit virus infectivity in cell culture. Significant type-, subtype-, and strain-specific variation in virus susceptibility to the synthetic inhibitors was observed. Among the viruses tested, H3 subtype strains evolved in humans since 1975 were the most sensitive, while the earlier H3 viruses and the type B strains were resistant. The virus-inhibitory potency of the polymeric sialosides correlated with their bindings to the virus, and was dependent on the virus affinity for the ligand, the density of the ligand, and the nature and molecular mass of the polymeric carrier. In embryonated eggs, the antiviral effect of poly(acryloyl-glycylamidobenzylsialoside-co-acrylic acid) was comparable to that of equine alpha 2-macroglobulin.

Antiviral Agents↗
PubMed1993

Probing of the receptor-binding sites of the H1 and H3 influenza A and influenza B virus hemagglutinins by synthetic and natural sialosides.

To compare features of the receptor-binding sites (RBSs) of different influenza virus hemagglutinins (HA), binding of a number of synthetic sialic acid (SA) analogs and natural sialosides by a panel of about 30 human influenza A and B virus strains was studied in a competitive ligand binding assay. For all the viruses tested, the N-acetyl group of Neu5Ac, as well as the natural orientation of the carboxylic group at C2 and the hydroxylic group at C4, was essential for binding. Significant type- and subtype-specific differences were observed in virus recognition of asialic parts of sialosides. H1 strains, unlike H3 and type B viruses, were found to bind alpha 2-6-sialyl-N-acetyllactosamine with about an order of magnitude higher affinity than alpha 2-6-sialyllactose (6'SL). The H1 viruses and the H3 strains with Gln in position 226 of HA, but not the H3 strains with Leu-226, bound 6'SL with a lower affinity than alpha 2-3-sialyllactose; this effect correlated clearly with the preferential binding by the former viruses of unsubstituted alpha Neu5Ac compared to methyl alpha-glycoside of Neu5Ac. Thus, differentiation between the types of the SA-Gal linkage by the A viruses appeared to depend, at least partially, upon the recognition by the HA of the first hydrocarbon group of the aglycon. Type B virus strains were distinct in having a lower affinity for the Neu5Ac moiety and in providing a higher contribution of the asialic portions of sialosides to the HA-ligand interactions. The last effects are presumably due to the amino acid insertions in the type B HA surrounding the RBS, which makes the receptor-binding pocket deeper. The results obtained in the present investigation indicate that while the functional groups of Neu5Ac studied are recognized by the RBSs of all influenza viruses, the magnitude of their contribution to the binding energy, as well as the contribution of the asialic portion of the receptor, may vary in dependence upon the virus type, subtype, and strain.

Amino Acid Sequence↗
PubMed1992

Influenza viruses differ in recognition of 4-O-acetyl substitution of sialic acid receptor determinant.

Equine alpha 2-macroglobulin (EM), known to contain both Neu5Ac and Neu4,5Ac2 sialic acid residues, was treated with Vibrio cholerae sialidase for the selective removal of Neu5Ac and was compared with the untreated EM for its binding by a panel of influenza viruses. Type A H3N2 virus strains having Leu in position 226 of their hemagglutinin (HA) changed the affinity for sialidase-treated EM only slightly, if at all, indicative of their ability to bind the 4-O-Ac-substituted Neu5Ac receptor determinant. At the same time, all B and H1N1 viruses, some H2N2 variants, as well as H3N2 strains with 226 Gln studied were unable to recognize Neu4,5Ac2 moieties of EM. Molecular modeling based on the known 3-D structure of H3 HA complexed with sialyllactose (Weis et al. (1988) Nature 333, 426-431) predicts that the 4-O-Ac substituent of sialic acid would protrude with its carbonyl oxygen inside the receptor-binding site of HA, thus possibly interfering with binding.

Carbohydrate Sequence↗
PubMed1992

A solid-phase enzyme-linked assay for influenza virus receptor-binding activity.

Receptor-binding properties of influenza viruses are usually characterized by the ability of viruses to interact with more or less defined sialic acid-containing carbohydrates, glycoproteins, or glycolipids assayed by haemagglutination (HA) or HA inhibition (HAI) tests. To overcome some drawbacks of these tests a solid-phase enzyme linked assay analogous to sandwich ELISA was developed. The virus is adsorbed specifically to the well of plastic microtitre plates coated with fetuin, and the binding of horseradish peroxidase (HRP)labelled sialylglycoproteins (SGPs) by the solid phase-attached virions is measured. The binding of unlabelled compounds is measured by competition with the attachment of a standard fetuin-HRP conjugate. The assay is easy to perform, quantitative (allows the determination of affinity constants), and sensitive (even the weak binding of free N-acetylneuraminic acid with Kd about 10(-1)-10(-2) M(-1) can be studied). Due to a higher stability of components of the present test system, as compared to red blood cells, the influence of pH, ionic strength, and other factors on virus-receptor interaction can also be investigated.

Evaluation Studies as Topic↗
PubMed1992

[Use of highly purified subvirion trivalent flue vaccine ("Grippovak") in groups with a high risk of complications].

During the epidemic season of 1989-1990 the subunit vaccine Grippovac was used in 20 asylums for old people and psychoneurological invalids in Moscow for the protection of the inhabitants and the personnel from influenza. Follow-up of the vaccinees during the period from November 1989 to March 1990 revealed that the use of this vaccine decreased the incidence of influenza-like diseases (ILD) 3.4-4.1 times among the vaccinees in comparison with that in the nonvaccinated control groups and significantly decreased the severity of the course of ILD, as well as the mortality because of ILD, among those vaccinees who had contacted ILD. This is indicative of good prospects of regular vaccinal prophylaxis of influenza at asylums for old people and other persons at a high risk of influenza complications.

Follow-Up Studies↗
PubMed1991

Recognition by human A and B influenza viruses of 8- and 7-carbon analogues of sialic acid modified in the polyhydroxyl side chain.

To evaluate the recognition by influenza viruses of the C9-C7 polyhydroxylated moiety of sialic acid (SA) receptor determinant a novel assay has been developed based on the assessment of binding by the solid-phase immobilized virus of the enzyme-labeled sialyglycoprotein fetuin treated by periodate or periodate/borohydride to contain an 8-carbon aldehyde, 7-carbon aldehyde, or corresponding hydroxyl analogues of SA. Some features of recognition by human influenza viruses of these SA analogues were type and subtype specific, especially marked differences being found between type A and type B viruses. At the same time a significant diversity was observed among virus strains belonging to the same subtype. The assay described provides a new tool for the differentiation of influenza viruses according to receptor binding properties and for an investigation of molecular interactions in the receptor binding site of the virus.

In Vitro Techniques↗
PubMed1990

Synthetic polymeric sialoside inhibitors of influenza virus receptor-binding activity.

Anomeric aminobenzylglycosides of Neu5Ac were coupled with the polyacrylate carrier and a number of synthetic polyvalent sialosides obtained were investigated as inhibitors of influenza virus attachment. The inhibitory activity of polymeric sialosides is highly dependent upon the Neu5Ac residue content and the nature of the carrier. The polyacrylic acid based polymer bearing 10 mol% of Neu5Ac is 3 orders of magnitude more potent inhibitor than the corresponding monovalent benzylsialoside and considerably more active than fetuin.

Antiviral Agents↗
PubMedDate not supplied

[The evaluation of the reactogenicity, harmlessness and prophylactic efficacy of Grippol trivalent polymer-subunit influenza vaccine administered to schoolchildren].

Vaccine "Grippol"--has been developed at the State Research Center--Institute of Immunology. The preparation belongs to new generation vaccines and is a trivalent polymer-subunit vaccine containing the sterile conjugate of influenza virus surface proteins, types A and B, bound with copolymer polyoxidonium. The administration of "Grippol" to children of school age (6-18 years) demonstrated low reactogenicity of the vaccine, its safety and sufficient prophylactic effectiveness. During observations on total morbidity (with the exception of influenza and acute respiratory diseases) no side effects produced by "Grippol" were registered. At the same time the fact that the morbidity rate of upper respiratory tract disease in the group of children immunized with the vaccine decreased in comparison with the control group (by 2.4 times) cannot be disregarded.

Adjuvants, Immunologic↗
PubMedDate not supplied

[Differences in receptor specificity between the influenza A viruses isolated from the duck, chicken, and human].

The affinity of the duck, chicken, and human influenza viruses to the host cell sialosides was determined, and considerable distinctions between duck and chicken viruses were found. Duck viruses bind to a wide range of sialosides, including the short-stem gangliosides. Most of the chicken viruses, like human ones, lose the ability to bind these gangliosides, which strictly correlates with the appearance of carbohydrate at position 158-160. The affinity of the chicken viruses to sialoglycoconjugates of chicken intestine as well as chicken, monkey, and human respiratory epithelial cells exceeds that of the duck viruses. The human influenza viruses have high affinity to the same cells but do not bind at all to the duck epithelial cell. This testifies to the absence of 6'-sialylgalactose residues from the duck cells, in contrast to chicken and monkey cells. The alteration of the receptor specificity of chicken viruses in comparison with duck ones results in the similarity of the patterns of accessible cells for chicken and human influenza viruses. This may be the cause of the appearance of the line of H9N2 viruses from Hong Kong live bird markets with receptor specificity similar to that of H3N2 human viruses, and of the ability of H5N1 and H9N2 chicken influenza viruses to infect humans.

Animals↗
PubMedDate not supplied

[The effect of losing glycosylation sites near the receptor-binding region on the receptor phenotype of the human influenza virus H1N1].

The receptor properties of influenza virus (IF) isolates/SSSR/90/77 are studied. The isolates are peculiar for losing glycosylation sites (GS) at the Asn131 receptor-binding region (GS131) after passaging in mice and at the Asn158 region (GS158) after cultivation in the presence of mouse serum. The loss of each carbohydrate residue increases the influenza virus affinity for carbohydrate chains with the terminal group Neu5Ac alpha 2-6Gal and reduces its affinity for Neu5Ac alpha 2-3Gal receptors. The effect is more pronounced in the GS158-depleted virus. Upon substitution of asparagine by aspartic acid, the electrostatic component of virus binding to the receptor is altered because of the increased negative charge on hemagglutinin. The virus receptor phenotype changes depending on the cultivation conditions. The isolate adapted to mice has higher affinity to mouse lung cell receptors, while the virus propagated in chick embryos in the presence of inhibitors has higher affinity to allantoic membrane cells.

Animals↗
PubMedDate not supplied

[Different receptor specificity of influence viruses from ducks and chickens and its reflection in the composition of sialosides on host cells and mucins].

The ability of influenza viruses from different hosts to bind to the intestinal epithelium of various birds (Anseriformes (Anatidae), Galliformes, Charadriiformes (sandpipers and sea gulls), Ciconiiformes (storks), Podicipediformes (grebes), and Gruiformes was studied. The composition of sialo-containing receptors on the epithelia was examined, by using lectins. Intestinal epitheliocytes of the Anatidae (Anseriformes) family was shown to have a low content of receptors binding both Sambucus nigra agglutinin (SNA) lectin specific to Siaalpha-6Gal, and Maackia amurensis agglutinin (MAA) lection specific to Siaalpha2-2Gal. Nevertheless, these cells well bound duck influenza viruses. The intestinal epithelium of Ciconiiformes, Podicipediformes, and Gruiformes well bound MMA lection, but avian influenza viruses weakly bound the latter. The intestinal cells of Gallinaceae bound both MMA and SNA lectins and avian and human influenza viruses. Thus, the composition of natural sialosides is different in various avian species whereas the receptor specificity of influenza viruses from various hosts reflects these differences. This can be accounted for by the differences in the ability of influenza viruses from different birds to break through the interspecies barrier, infecting mammals and human beings in particular.

Animals↗