Hasan Kweder, Michelle Ainouze, Sara Louise Cosby, et al., ?Mutations in the H, F, or M Proteins Can Facilitate Resistance of Measles Virus to Neutralizing Human Anti-MV Sera,? Advances in Virology, vol. 2014, Article ID 205617, 18 pages, 2014. doi:10.1155/2014/205617
Copyright ? 2014 Hasan Kweder et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV?s resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.
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MV is a serologically monotypic virus and in theory, vaccination should provide life-long protection. However, the proportion of the population possessing only vaccine-induced immunity has increased over time with reduced exposure to wild-type MV infection and there is now evidence of resistance of recent measles virus wild-type isolates to antibody-mediated neutralization in vaccinees. This includes individuals with not only primary but also secondary vaccine failure [7, 8] and is a concern for global MV elimination. It is evident that a better understanding of the molecular basis of MV?s escape from neutralizing antibody is required...
Copyright ? 2014 Hasan Kweder et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV?s resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.
...
MV is a serologically monotypic virus and in theory, vaccination should provide life-long protection. However, the proportion of the population possessing only vaccine-induced immunity has increased over time with reduced exposure to wild-type MV infection and there is now evidence of resistance of recent measles virus wild-type isolates to antibody-mediated neutralization in vaccinees. This includes individuals with not only primary but also secondary vaccine failure [7, 8] and is a concern for global MV elimination. It is evident that a better understanding of the molecular basis of MV?s escape from neutralizing antibody is required...