Structural basis of immune recognition of influenza virus hemagglutinin.
TL;DR: An article de synthese sur the structure and the fonction de l'hemagglutinine (HA), la variation naturelle de l'sHA, les reponses des cellules B and T a l'HA, la neutralisation du virus, and l'immunite apportee par les vaccins.
Abstract: Article de synthese sur la structure et la fonction de l'hemagglutinine (HA), la variation naturelle de l'HA, les reponses des cellules B et T a l'HA, la neutralisation du virus, et l'immunite apportee par les vaccins
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TL;DR: It is shown that a genome-wide duplication post-dates the divergence of Arabidopsis from most dicots, and that additional, more ancient duplication events affect more distant taxonomic comparisons.
Abstract: Conservation of gene order in vertebrates is evident after hundreds of millions of years of divergence, but comparisons of the Arabidopsis thaliana sequence to partial gene orders of other angiosperms (flowering plants) sharing common ancestry approximately 170-235 million years ago yield conflicting results. This difference may be largely due to the propensity of angiosperms to undergo chromosomal duplication ('polyploidization') and subsequent gene loss ('diploidization'); these evolutionary mechanisms have profound consequences for comparative biology. Here we integrate a phylogenetic approach (relating chromosomal duplications to the tree of life) with a genomic approach (mitigating information lost to diploidization) to show that a genome-wide duplication post-dates the divergence of Arabidopsis from most dicots. We also show that an inferred ancestral gene order for Arabidopsis reveals more synteny with other dicots (exemplified by cotton), and that additional, more ancient duplication events affect more distant taxonomic comparisons. By using partial sequence data for many diverse taxa to better relate the evolutionary history of completely sequenced genomes to the tree of life, we foster comparative approaches to the study of genome organization, consequences of polyploidy, and the molecular basis of quantitative traits.
1,420 citations
TL;DR: By matching model output to phylogenetic patterns seen in sequence data collected through global surveillance, it is found that short-lived strain-transcending immunity is essential to restrict viral diversity in the host population and thus to explain key aspects of drift and shift dynamics.
Abstract: In pandemic and epidemic forms, influenza causes substantial, sometimes catastrophic, morbidity and mortality. Intense selection from the host immune system drives antigenic change in influenza A and B, resulting in continuous replacement of circulating strains with new variants able to re-infect hosts immune to earlier types. This ‘antigenic drift’1 often requires a new vaccine to be formulated before each annual epidemic. However, given the high transmissibility and mutation rate of influenza, the constancy of genetic diversity within lineages over time is paradoxical. Another enigma is the replacement of existing strains during a global pandemic caused by ‘antigenic shift’—the introduction of a new avian influenza A subtype into the human population1. Here we explore ecological and immunological factors underlying these patterns using a mathematical model capturing both realistic epidemiological dynamics and viral evolution at the sequence level. By matching model output to phylogenetic patterns seen in sequence data collected through global surveillance2, we find that short-lived strain-transcending immunity is essential to restrict viral diversity in the host population and thus to explain key aspects of drift and shift dynamics.
682 citations
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...These assumptions reflect empirical studies suggesting that two or more substitutions at key antigenic sites are required to escape pre-existing immunit...
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TL;DR: Monitoring new H3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drift.
Abstract: Eighteen codons in the HA1 domain of the hemagglutinin genes of human influenza A subtype H3 appear to be under positive selection to change the amino acid they encode. Retrospective tests show that viral lineages undergoing the greatest number of mutations in the positively selected codons were the progenitors of future H3 lineages in 9 of 11 recent influenza seasons. Codons under positive selection were associated with antibody combining site A or B or the sialic acid receptor binding site. However, not all codons in these sites had predictive value. Monitoring new H3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drift.
511 citations
TL;DR: The findings of Koel et al. (p. 976) show that major antigenic change can be caused by single amino acid substitutions, which substantially skew the way the immune system “sees” the virus.
Abstract: The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.
486 citations
TL;DR: Findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.
Abstract: The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1-H16) The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate The mAbs used different VH genes and carried a high frequency of somatic mutations With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid-sensitive epitopes in the HA stem region Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus
455 citations