Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetics of synthesis and the nature of the oligosaccharides of the glycoproteins of pneumonia virus of mice (PVM) were studied. Tryptic peptide mapping showed that the two major glycosylated polypeptides G1 and G2 were different forms of the same protein. G2 was derived from G1 which in turn appeared to be derived from an unidentified precursor. The G1/G2 protein of PVM is probably a haemagglutinin since a monoclonal antibody directed against it has a high haemagglutination inhibition titre. On the basis of experiments with inhibitors and glycosidases it was deduced that G1 and G2 have both N-linked and O-linked oligosaccharides. The putative fusion protein-equivalent of PVM was shown to possess N-linked oligosaccharides. In the presence of tunicamycin a high mobility form (F1t) appeared to be derived from a precursor (F0t) with the same mobility as the fully glycosylated protein. If by analogy with other paramyxoviruses this represents a cleavage event, the difference in mobility of the precursor and product suggests that the putative F2 product is smaller than the corresponding F2 protein of other paramyxoviruses. However, no F2 candidate protein was detected and evidence for an F1,2 dimer was inconclusive. The glycoproteins of PVM resemble those of respiratory syncytial virus in terms of their pattern of glycosylation, but differ in their processing.
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PMID:Polypeptides of pneumonia virus of mice. II. Characterization of the glycoproteins. 273 20

Relatively little is known about the viral factors contributing to the lethality of the 1918 pandemic, although its unparalleled virulence was likely due in part to the newly discovered PB1-F2 protein. This protein, while unnecessary for replication, increases apoptosis in monocytes, alters viral polymerase activity in vitro, enhances inflammation and increases secondary pneumonia in vivo. However, the effects the PB1-F2 protein have in vivo remain unclear. To address the mechanisms involved, we intranasally infected groups of mice with either influenza A virus PR8 or a genetically engineered virus that expresses the 1918 PB1-F2 protein on a PR8 background, PR8-PB1-F2(1918). Mice inoculated with PR8 had viral concentrations peaking at 72 hours, while those infected with PR8-PB1-F2(1918) reached peak concentrations earlier, 48 hours. Mice given PR8-PB1-F2(1918) also showed a faster decline in viral loads. We fit a mathematical model to these data to estimate parameter values. The model supports a higher viral production rate per cell and a higher infected cell death rate with the PR8-PB1-F2(1918) virus. We discuss the implications these mechanisms have during an infection with a virus expressing a virulent PB1-F2 on the possibility of a pandemic and on the importance of antiviral treatments.
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PMID:Effect of 1918 PB1-F2 expression on influenza A virus infection kinetics. 2137 24

The PB1-F2 protein encoded by influenza A viruses can contribute to virulence, a feature that is dependent of its sequence polymorphism. Whereas PB1-F2 from some H1N1 viruses were shown to exacerbate the inflammatory response within the airways, the contribution of PB1-F2 to highly pathogenic avian influenza virus (HPAIV) virulence in mammals remains poorly described. Using a H5N1 HPAIV strain isolated from duck and its PB1-F2 knocked-out mutant, we characterized the dynamics of PB1-F2-associated host response in a murine model of lethal pneumonia. The mean time of death was 10 days for the two viruses, allowing us to perform global transcriptomic analyses and detailed histological investigations of the infected lungs at multiple time points. At day 2 post-infection (pi), while no histopathological lesion was observed, PB1-F2 expression resulted in a significant inhibition of cellular pathways involved in macrophage activation and in a transcriptomic signature suggesting that it promotes damage to the epithelial barrier. At day 4 pi, the gene profile associated with PB1-F2 expression revealed dysfunctions in NK cells activity. At day 8 pi, PB1-F2 expression was strongly associated with increased transcription of genes encoding chemokines and cytokines implicated in the recruitment of granulocytes, as well as expression of a number of genes encoding enzymes expressed by neutrophils. These transcriptomic data were fully supported by the histopathological analysis of the mice lungs which evidenced more severe inflammatory lesions and enhanced recruitment of neutrophils in the context of PB1-F2 expression, and thus provided a functional corroboration to the insight obtained in this work. In summary, our study shows that PB1-F2 of H5N1 HPAIV markedly influences the expression of the host transcriptome in a different way than its H1N1 counterparts: H5N1 PB1-F2 first delays the initial immune response but increases the pulmonary inflammatory response during the late stages of infection.
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PMID:Kinetic characterization of PB1-F2-mediated immunopathology during highly pathogenic avian H5N1 influenza virus infection. 2346 51