How to be good at being a virus: Biochemical constraints of viral life-history evolution

Thomas Berngruber

    Research output: ThesisThesis fully internal (DIV)

    805 Downloads (Pure)

    Abstract

    Viral reproduction depends on a careful balance of the viral life-cycle in time and magnitude. Maintenance of this balance is granted by the regulation of viral protein production and protein interactions. Viral evolution therefore hinges on the possibilities to optimize these protein interactions. In many viral systems, these possibilities are limited, especially for cases in which the beneficial activity of a protein is associated with detrimental side effect – a situation that is termed molecular trade-off. Goals of this thesis is the derivation of molecular trade-offs for various groups of viruses, prediction of their consequence for viral evolution and testing of these predictions in experimental evolution.
    This approach is demonstrated in four examples: 1) the conflicting effects on viral replication and packaging proteins for the early an late life-cycle of phage MS2, 2) the detrimental effect of viral attachment rate on epidemic spread in phage ΦX174, 3) molecular control of virulence in phage λ an its side effect on superinfection inhibition and 4) the antagonistic effects of the receptor destroying enzyme, neuraminidase, of influenza virus. The essence of our approach is the reduction of the full biochemical complexity of viral development into a simplified representation of the viral life cycle that allows the identification of the biochemical steps which are strongly linked to viral fitness. By this approach we point out the evolutionary Achilles heel of a viral system. By characterizing these evolutionary weaknesses of a viral system we aim to provide a stronghold for the development of future anti-viral strategies.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Supervisors/Advisors
    • Weissing, Franz, Supervisor
    Award date3-Jan-0001
    Publisher
    Publication statusPublished - 2008

    Keywords

    • Proefschriften (vorm)
    • Moleculaire evolutie, Virulentie , Gastheren, Wiskundige mod
    • biochemie: overige
    • virologie (biologie)
    • infectieziekten, parasitaire ziekten

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