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- Crystal growth (2)
- Adaption (1)
- Cordierite (1)
- DNA polymerase (1)
- Diopside (1)
- Glass (1)
- Hypermutation (1)
- Kinetik (1)
- Kristallwachstumsgeschwindigkeit (1)
- Marek's Disease Virus (1)
Organisationseinheit der BAM
Evolution relies on the availability of genetic diversity for fitness-based selection. However, most deoxyribonucleic acid (DNA) viruses employ DNA polymerases (Pol) capable of exonucleolytic proofreading to limit mutation rates during DNA replication. The relative genetic stability produced by high-fidelity genome replication can make studying DNA virus adaptation and evolution an intensive endeavor, especially in slowly replicating viruses. Here, we present a proofreading-impaired Pol mutant (Y547S) of Marek’s disease virus that exhibits a hypermutator phenotype while maintaining unimpaired growth in vitro and wild-type (WT)-like pathogenicity in vivo. At the same time, mutation frequencies observed in Y547S virus populations are 2–5-fold higher compared to the parental WT virus. We find that Y547S adapts faster to growth in originally non-permissive cells, evades pressure conferred by antiviral inhibitors more efficiently, and is more easily attenuated by serial passage in cultured cells compared to WT. Our results suggest that hypermutator viruses can serve as a tool to accelerate evolutionary processes and help identify key genetic changes required for adaptation to novel host cells and resistance to antiviral therapy. Similarly, the rapid attenuation achieved through adaptation of hypermutators to growth in cell culture enables identification of genetic changes underlying attenuation and virulence, knowledge that could practically exploited, e.g. in the rational design of vaccines.
We measured and collected literature data for the crystal growth rate, u(T), of µ-cordierite (2MgO · 2Al2O3 · 5SiO2) and diopside (CaO · MgO · 2SiO2) in their isochemical glass forming melts. The data cover exceptionally wide temperature ranges, i.e. 8001350 °C for cordierite and 7501378 °C for diopside. The maximum of u(T) occurs at about 1250 °C for both systems. A smooth shoulder is observed around 970 °C for µ-cordierite. Based on measured and collected viscosity data, we fitted u(T) using standard crystal growth models. For diopside, the experimental u(T) fits well to the 2D surface nucleation model and also to the screw dislocation growth mechanism. However, the screw dislocation model yields parameters of more significant physical meaning. For cordierite, these two models also describe the experimental growth rates. However, the best fittings of u(T) including the observed shoulder, were attained for a combined mechanism, assuming that the melt/crystal interface growing from screw dislocations is additionally roughened by superimposed 2D surface nucleation at large undercoolings, starting at a temperature around the shoulder. The good fittings indicate that viscosity can be used to assess the transport mechanism that determines crystal growth in these two systems, from the melting point Tm down to about Tg, with no sign of a breakdown of the StokesEinstein/Eyring equation.