Hepatitis B virus Raw sequence reads

Human hepatitis B virus (HBV) is a small DNA virus (around 3.2 Kbp). The circulating form of its genome is held in a relaxed-circular configuration (rcDNA), stabilized via complementarity at the 5-prime ends of both DNA strands since neither of them is covalently closed. When rcDNA is delivered to the nucleus, it is repaired and covalently closed circular DNA (cccDNA) is generated. This form of viral genome is a very stable nuclear episome which serves as the template for the transcription of all viral RNAs, by the host RNA Pol II. To a lesser extent, HBV-DNA can integrate into the host genome, although it is not necessary for HBV replication. One of viral RNAs, the pregenomic RNA (pgRNA), serves as the template for viral polymerase to produce new rcDNA via reverse transcription. The viral polymerase lacks proofreading activity, and together with the intense replicative activity and small genome size of HBV, results in a high degree of genetic variability. In addition, certain host factors (e.g. APOBEC3 cytidine deaminase family) are reported to be associated with hypermutational activity. All these factors yield an HBV quasispecies, provided with a great plasticity and capacity for rapid adaptation to the environmental pressures due to the immune response or antiviral treatments.The aim of this project is to use next-generation sequencing technologies to analyze the variability of HBV genome in regions relevant for its replication, pathogenesis or as targets for directed gene therapy.