muramidase and Orthomyxoviridae-Infections

There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with influenza virus neuraminidase, and three Fab complexes with their anti-idiotype Fabs. The pattern of binding that emerges is similar to that found with other protein-protein interactions, with good shape complementarity between the interacting surfaces and reasonable juxtapositions of polar residues so as to permit hydrogen-bond formation. Water molecules have been observed in cavities within the interface and on the periphery, where they often form bridging hydrogen bonds between antibody and antigen. For the most part the antigen is bound in the middle of the antibody combining site with most of the six complementarity-determining residues involved in binding. For the most studied antigen, lysozyme, the epitopes for four antibodies occupy approximately 45% of the accessible surface area. Some conformational changes have been observed to accompany binding in both the antibody and the antigen, although most of the information on conformational change in the latter comes from studies of complexes with small antigens.

Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antigen-Antibody Reactions; Antigens, Viral; Bacterial Proteins; Binding Sites, Antibody; Chickens; Epitope Mapping; Epitopes; Immunoglobulin Fab Fragments; Mice; Models, Molecular; Muramidase; Neuraminidase; Orthomyxoviridae Infections; Phosphoenolpyruvate Sugar Phosphotransferase System; Protein Binding; Protein Conformation; Structure-Activity Relationship; X-Ray Diffraction

Intranasal infection of outbred male mice with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus led to high (85%) mortality of animals. Morphological studies of liver specimens showed destructive changes in the parenchyma (93.5% hepatocytes), caused by long persistence of the virus in the liver. The virus persistence was conjugated with activation of cellular immunity, manifesting by an increase in the counts of cells with high expression of proinflammatory cytokines (TNF-α) and lysosomal enzymes (lysozyme, cathepsin D). Injections of oxidized dextran 3 and 1 days before infection reduced mortality and 2-fold attenuated destructive changes in the liver, presumably due to prevention of virus penetration into the target cells, modulation of immune reactions, and stimulation of reparative plastic processes.

Topics: Animals; Cathepsin D; Cytokines; Dextrans; Histological Techniques; Immunohistochemistry; Influenza A Virus, H5N1 Subtype; Liver; Male; Mice; Muramidase; Organ Size; Orthomyxoviridae Infections; Regeneration

To maintain homeostasis of the immune system is considered important for the prevention of influenza A virus infection. Aberrant systemic inflammation is frequently induced by influenza A virus infection, and the severity of the symptoms is associated with pathogenicity of the virus. Lactic acid bacteria are known to have a positive effect in maintaining the immune system. Furthermore, preparations of a lactic acid bacteria strain, Enterococcus faecalis FK-23 (FK-23), have been reported to exert preferable homeostatic effects on immune diseases such as allergic rhinitis and early asthmatic responses. In this study, we examined the efficacy of the water-soluble fraction of lysed and heat-treated FK-23 (SLFK) against a lethal influenza A virus challenge. Mice were orally administered SLFK from day -7 to day 20, and intranasally infected with influenza virus A/Puerto Rico/8/34 (H1N1) at 10(3) PFU on day 0. The survival rate of SLFK-administered mice after influenza A virus infection was significantly improved compared with that of control mice. In addition, the mRNA expression level of the anti-inflammatory cytokine interleukin-10 (IL-10) in lung tissues was enhanced by the oral administration of SLFK after influenza A virus infection. These observations suggest that the oral administration of SLFK exerts a protective effect against influenza virus infection through the activation of the anti-inflammatory response.

Topics: Administration, Oral; Animals; Enterococcus faecalis; Hot Temperature; Influenza A Virus, H1N1 Subtype; Interleukin-10; Lung; Male; Mice; Mice, Inbred C57BL; Muramidase; Orthomyxoviridae Infections; Survival Rate

C57Bl/6 mice were intranasally infected with influenza virus A/H5N1 A/goose/Krasnoozerskoye/627/05. The mortality rate of animals reached 70% on day 14 of the disease. The lungs of animals were characterized by necroses, destruction of vessels, hemorrhagic and thrombotic complications, edematous syndrome, and early fibrosis of the interstitium. On days 6-10 after infection, fibrosis was found in the zones of postnecrotic inflammatory infiltration. The expression of lysozyme and myeloperoxidase by pulmonary macrophages was initially increased, but decreased on day 10 of the study. The number of cathepsin D-expressing macrophages was elevated up to the 10th day of examination.

Topics: Animals; Cathepsin D; Disease Models, Animal; Fas-Associated Death Domain Protein; Influenza A Virus, H5N1 Subtype; Interleukin-6; Lung; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Muramidase; Nitric Oxide Synthase Type II; Orthomyxoviridae Infections; Peroxidase; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha

Severe pneumonia is found in simultaneous influenza pneumonia and bacterial infection, and suggests a relationship with immunological mechanisms. Here, we performed two-dimensional gel electrophoresis to detect immunological molecules related to the fulminant pneumonia caused by influenza virus and Streptococcus pneumoniae co-infection in mice. We found two spots that were expressed strongly in co-infected mouse lungs, compared with S. pneumoniae or influenza virus singly infected mouse lungs. The spots were analysed by mass spectrometry, and identified as alpha-1 anti-trypsin (A1AT), known as an anti-protease for neutrophil-derived proteolytic enzymes, and creatine kinase, which reflects a greater degree of lung damage and cell death. A1AT expression was increased significantly, and proteolytic enzymes from neutrophils, such as neutrophil elastase, myeloperoxidase and lysozyme, were also secreted abundantly in influenza virus and S. pneumoniae co-infected lungs compared with S. pneumoniae or influenza virus singly infected lungs. These data suggest that A1AT may play a central role as a molecule with broad anti-inflammatory properties, and regulation of the neutrophil-mediated severe lung inflammation is important in the pathogenesis of co-infection with influenza virus and bacteria.

Topics: alpha 1-Antitrypsin; Animals; Bronchoalveolar Lavage Fluid; Chemokine CXCL2; Creatine Kinase; Disease Susceptibility; Electrophoresis, Gel, Two-Dimensional; Influenza A virus; Leukocyte Elastase; Lung; Male; Mice; Mice, Inbred CBA; Muramidase; Orthomyxoviridae Infections; Peroxidase; Pneumonia, Pneumococcal; Pneumonia, Viral

We established a mouse model in which fatal pneumonia was induced by pneumococcal superinfection following influenza virus infection in chronic Pseudomonas aeruginosa infected mice. In this mouse model, influenza virus infection caused a significant increase in inflammatory cells, cytokines and severe tissue damage in the lungs of these P. aeruginosa infected mice, before pneumococcal infection. Intrapulmonary virus titres were significantly increased in mice with chronic P. aeruginosa infection, compared with control mice. Neutrophil function analysis showed significant reduction of myeloperoxidase (MPO) activity and lysozyme secretion by influenza virus infection in these mice. Our results suggest that influenza virus infection may play an important role in inducing pneumococcal pneumonia in chronic P. aeruginosa infected mice. Our results suggested that our mouse model is useful for investigating the pathogenesis of influenza virus infection in patients with chronic lung infection.

Topics: Acute Disease; Animals; Chronic Disease; Colony Count, Microbial; Cytokines; Disease Models, Animal; Disease Susceptibility; Lung; Lung Diseases, Parasitic; Male; Mice; Mice, Inbred Strains; Muramidase; Orthomyxoviridae Infections; Peroxidase; Pneumococcal Infections; Pneumonia, Pneumococcal; Pseudomonas Infections; Superinfection

Topics: Animals; Blood Bactericidal Activity; Depression, Chemical; Dose-Response Relationship, Drug; Immunity; Leukocytes; Mice; Muramidase; Orthomyxoviridae Infections; Phagocytosis; Properdin; Rabbits; Time Factors; Vitamin A; Vitamins

Topics: Animals; Disease Models, Animal; Drug Synergism; Encephalomyocarditis virus; Female; Injections, Intraperitoneal; Injections, Intravenous; Leukocyte Count; Male; Mice; Muramidase; Orthomyxoviridae; Orthomyxoviridae Infections; Phagocytosis; Phenanthrenes; Poliomyelitis; Salmonella Infections, Animal; Salmonella typhimurium; Staphylococcal Infections; Staphylococcus

Topics: Bronchitis; Chloramphenicol; Humans; Infant; Influenza, Human; Muramidase; Orthomyxoviridae; Orthomyxoviridae Infections; Rhinitis; Streptomycin; Tracheitis