Inhibition of glycoprotein biosynthesis of influenza virus by D-glucosamine and 2-deoxy-D-glucose.
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Biomedical subjects
Publications and source records attributed to H D Klenk.
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Vesicular stomatitis virions grown in baby hamster kidney (BHK-21-F) cells were found to contain hematoside (neuraminosyl-galactosyl-glucosyl-ceramide). This ganglioside, which was the only detectable glycolipid in the virion, is also the only glycolipid found in significant amount in BHK-21-F cells. Approximately 87% of the total neuraminic acid in the virion was found to be linked to protein and 13% to lipid.
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Glycosphingolipids of rhesus monkey kidney (MK), bovine kidney (MDBK), and two lines of hamster kidney (BHK21-F and Hak) cells have been compared with those of parainfluenza (SV5) virions grow in these cells. There are qualitative and quantitative differences in the neutral glycolipids and gangliosides found in the various cells. Cells with a high neutral glycolipid content (MK and MDBK) contain little or no gangliosides, and those with a relatively high ganglioside content (BHK21-F and HaK) contain little neutral glycolipid. Glycosphingolipids are found predominantly in the plasma membranes. Neutral glycolipids of the host cell membrane are incorporated into the envelope of SV5 virions, but neither gangliosides nor protein-bound neuraminic acid are found in virions. The absence of neuraminic acid from the virion may be due to the action of viral neuraminidase.
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In influenza the combined virus-bacterial pneumonia is approximately three times more common than primary viral pneumonia. The bacteria most commonly involved are Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae. S. aureus co-infection is reported to have a fatality rate of up to 42% (ref. 2). It is thought that virus infection in the respiratory tract favours growth conditions for bacteria. In this letter data are presented which show that some S. aureus strains secrete a protease which exerts a decisive influence on the outcome of influenza virus infection in mice by cleavage activation of the virus haemagglutinin.
Antibodies specific to the N-terminal 34-aminoacid peptide of the major nucleocapsid protein NP of human influenza A viruses were obtained. The NP proteolytic cleavage occurring in infected cells late in infection has been demonstrated using this antibody. The antibody specifically reacted with noncleaved NP of 56 kD m.w. but not with cleaved NP of 53 kD m.w. This indicates that NP56-->NP53 intracellular cleavage released the N-terminal 3 kD peptide of Np molecule. The released 3 kD peptide did not accumulate in infected cells. Since the RNA-binding and nucleus migrating signals are located in the N-terminus of NP molecule, presumably, the terminal cleavage is important for intracellular NP functions.