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Jennifer Risso-Ballester defends her doctoral thesis on the genomic instability of DNA viruses

  • October 29th, 2019
Jennifer Risso-Ballester and Rafael Sanjuán
Jennifer Risso-Ballester and Rafael Sanjuán

This doctoral thesis, supervised by Rafael Sanjuán, evaluates mutation rates of DNA viruses using advanced sequencing techniques and studies how viruses evade host repair mechanisms. The results of the thesis have been published in journals such as PLoS Pathogens and Viruses. The thesis was defended on October 29, 2019.

DNA viruses are very abundant, but it is often thought that their degree of genetic diversity and adaptability is much lower than that of RNA viruses due to lower mutation rates. However, there is very little information on mutation rates of DNA viruses, probably because new generation sequencing (NGS) technologies often have error rates that are orders of magnitude higher than the mutation rates to be estimated. Consequently, the only mutation rates currently available are based on the annotation of phenotypes associated with known mutations. However, recent developments in NGS, specifically a new technique called duplex sequencing (DS), improve accuracy by about four orders of magnitude compared to other conventional NGS methods.

One of the main objectives of the thesis, entitled "Regulation of the mutation rate in DNA viruses" was the study of the appearance of spontaneous mutations using DS to determine the mutation rate of our DNA model virus, the human adenovirus type 5 (HAdV5). On the other hand, mutation rates in viruses depend not only on the fidelity of the polymerases used during replication but also on other factors such as genome repair efficiency. The cellular DNA repair system (DDR) is very efficient and takes care of restoring both the errors that have originated during replication and the repair of damaged DNA. The development of strategies by viruses to evade these DNA repair systems would result in an increase in mutation frequency. Numerous studies have demonstrated the interaction between eukaryotic DNA viruses and DDR. However, the possible consequences of this virus-host interaction on the mutation rate of the virus are unknown. Access to DDR would justify the low mutation rates observed in DNA viruses while also explaining the observed differences between RNA and DNA viruses. To address this issue, this research used experimental evolution with non-tumor cells and chemical inhibitors to suppress the modulators of the main DDR pathways. SD allowed the resulting genetic diversity in the virus genome to be evaluated.

Jennifer Risso-Ballester’s doctoral thesis was developed in the Virus Experimental Evolution group at I2SysBio under the supervision of Rafael Sanjuán (Professor of Genetics at the University of Valencia). Pilar Domingo Calap and Santiago Elena Fito (both members of I2SysBio) and F. Xavier López Labrador (Joint Research Unit FISABIO-I2SysBio Evolution and Health) were the tribunal members.

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