The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus

<p>Abstract</p> <p>Background</p> <p>Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity.</p> <p>Methods</p> <p>The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results.</p> <p>Results</p> <p>Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3) deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time.</p> <p>Conclusions</p> <p>Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.</p

The nonlinear time-dependent response of isotactic polypropylene

Tensile creep tests, tensile relaxation tests and a tensile test with a constant rate of strain are performed on injection-molded isotactic polypropylene at room temperature in the vicinity of the yield point. A constitutive model is derived for the time-dependent behavior of semi-crystalline polymers. A polymer is treated as an equivalent network of chains bridged by permanent junctions. The network is modelled as an ensemble of passive meso-regions (with affine nodes) and active meso-domains (where junctions slip with respect to their positions in the bulk medium with various rates). The distribution of activation energies for sliding in active meso-regions is described by a random energy model. Adjustable parameters in the stress--strain relations are found by fitting experimental data. It is demonstrated that the concentration of active meso-domains monotonically grows with strain, whereas the average potential energy for sliding of junctions and the standard deviation of activation energies suffer substantial drops at the yield point. With reference to the concept of dual population of crystalline lamellae, these changes in material parameters are attributed to transition from breakage of subsidiary (thin) lamellae in the sub-yield region to fragmentation of primary (thick) lamellae in the post-yield region of deformation.Comment: 29 pages, 12 figure

Fractured metallic tracheostomy tube in a child: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Tracheostomy is a common airway procedure for life support. The fracture of the tracheostomy tube is a rare complication. We report a case of a 14-year-old boy whose fractured stainless steel tracheostomy tube dislodged into the tracheobronchial tree. We include a literature review and proposed recommendations for tracheostomy care.</p> <p>Case presentation</p> <p>A 14-year-old Thai boy who had a stainless steel tracheostomy tube presented with a complaint of intermittent cough for 2 months. During tracheostomy tube cleaning, his parents found that the inner tube was missing. A chest X-ray revealed a metallic density foreign body in his right main bronchus. He underwent bronchoscopic removal of the inner tracheostomy tube and was discharged without further complications.</p> <p>Conclusion</p> <p>A fractured tracheostomy tube is a rare complication. Appropriate cleaning and scheduled replacement of the tracheostomy tube may prevent this complication.</p

Human Metapneumovirus Glycoprotein G Inhibits Innate Immune Responses

Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infection in infants, as well as in the elderly and immunocompromised patients. No effective treatment or vaccine for hMPV is currently available. A recombinant hMPV lacking the G protein (rhMPV-ΔG) was recently developed as a potential vaccine candidate and shown to be attenuated in the respiratory tract of a rodent model of infection. The mechanism of its attenuation, as well as the role of G protein in modulation of hMPV-induced cellular responses in vitro, as well as in vivo, is currently unknown. In this study, we found that rhMPV-ΔG-infected airway epithelial cells produced higher levels of chemokines and type I interferon (IFN) compared to cells infected with rhMPV-WT. Infection of airway epithelial cells with rhMPV-ΔG enhanced activation of transcription factors belonging to the nuclear factor (NF)-κB and interferon regulatory factor (IRF) families, as revealed by increased nuclear translocation and/or phosphorylation of these transcription factors. Compared to rhMPV-WT, rhMPV-ΔG also increased IRF- and NF-κB-dependent gene transcription, which was reversely inhibited by G protein expression. Since RNA helicases have been shown to play a fundamental role in initiating viral-induced cellular signaling, we investigated whether retinoic induced gene (RIG)-I was the target of G protein inhibitory activity. We found that indeed G protein associated with RIG-I and inhibited RIG-I-dependent gene transcription, identifying an important mechanism by which hMPV affects innate immune responses. This is the first study investigating the role of hMPV G protein in cellular signaling and identifies G as an important virulence factor, as it inhibits the production of important immune and antiviral mediators by targeting RIG-I, a major intracellular viral RNA sensor