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  • Title: Isolation and characterization of NMSO3-resistant mutants of respiratory syncytial virus.
    Author: Kimura K, Ishioka K, Hashimoto K, Mori S, Suzutani T, Bowlin TL, Shigeta S.
    Journal: Antiviral Res; 2004 Mar; 61(3):165-71. PubMed ID: 15168797.
    Abstract:
    We obtained two mutant strains of respiratory syncytial virus (RSV) which showed resistance against NMSO3 after 15 and 33 passages, respectively, in HEp-2 cells in the presence of 6.8 microM of NMSO3. The EC50 values of NMSO3 for the resistant virus strains were 0.48 and 0.93 microM, that is 4.8-9.3 times higher than that of the parent strain (EC50 = 0.1 microM). The most resistant strain also showed resistance against heparin but was sensitive to dextran sulfate and a polyoxotungstate, PM-523. In order to determine whether the acquisition of resistance to NMSO3 was the result of the accumulation of genetic changes of virus, we sequenced the G- and F-protein genes. In comparison with the standard type of RSV strains, we identified changes of 10 amino acids in the G protein including those at the central conserved segment. However, we did not observe any particular changes in the amino acid sequence of the F-protein of the resistant strains. From these results, we conclude that NMSO3 inhibits the G-protein interaction to the receptor. The mutations in the G-protein may result in the observed phenotypic resistance of RSV towards NMSO3.
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