Genetic diversity and geographic patterns of human herpesvirus 4 and 6

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• dc.contributor.author Telford, Marco
• dc.contributor.other Navarro, Arcadi
• dc.contributor.other Santpere Baró, Gabriel
• dc.contributor.other Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
• dc.date.accessioned 2024-03-16T02:34:07Z
• dc.date.available 2024-03-16T02:34:07Z
• dc.date.issued 2018-12-20T15:37:48Z
• dc.date.issued 2019-12-19T00:00:10Z
• dc.date.issued 2017-12-19
• dc.date.modified 2024-03-15T10:57:17Z
• dc.description.abstract This thesis focuses on Human herpesvirus 4 and 6, two ubiquitous viruses with a long list of putative disease associations, ranging from malignancies such as lymphomas and carcinomas to multiple sclerosis. To date, the relatively limited genetic data on these organisms hinders the understanding of their variability and their genetic structure at a population level. We here explore wet lab techniques for the production of genetic data in a cost-effective manner in order to reach the order of magnitude that is required to unravel the genetics these viruses. After successfully identifying individuals affected by integrated chromosomally inherited human herpesvirus 6 from public datasets of sequencing data, the sequences of the infecting virus were produced by target enrichment means from the source biological sample. The testing of an in-house target enrichment protocol followed, aiming to target latently infecting virus in human saliva. While the protocol still needs optimization and the aid of alternative techniques to be suitable for cost-effective, large-scale studies, the results were very satisfactory (up to >800-fold enrichment). In parallel, long range PCRs were used to produce human herpesvirus 4 latency genes sequences from one large human healthy saliva panel including populations previously unexplored in terms of human herpesvirus 4 isolates. Thanks to the combination of wet lab techniques and data analysis, the presence of genetic patterns in the two studied viruses is emerging, with human herpesvirus 6 presenting differences in diversity between its two species, as well as signs of geographical patterns possibly in part hidden by recombination events. Different bioinformatics approaches showed instead a stronger geographical stratification in human herpesvirus 4, with regional-driven clades. This information would allow us for a correct study design when addressing the relationship between virus and disease, taking into account the natural variation of the virus, as well as help to pinpoint genetic features that might be determinant for disease triggering or development. The strong geographical patterns presented by the diseases associated to these viruses strengthen the notion of the importance of this investigation and opens an avenue of research focused on disclosing the putative relationship between viruses strain variation and the risk for these virus–associated diseases.
• dc.description.abstract Programa de doctorat en Biomedicina
• dc.format 220 p.
• dc.format application/pdf
• dc.format application/pdf
• dc.identifier http://hdl.handle.net/10803/664509
• dc.identifier.uri http://hdl.handle.net/10230/36180
• dc.language.iso eng
• dc.publisher Universitat Pompeu Fabra
• dc.rights ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.
• dc.rights info:eu-repo/semantics/openAccess
• dc.source TDX (Tesis Doctorals en Xarxa)
• dc.subject.keyword Human herpesvirus 4
• dc.subject.keyword Human Herpesvirus 6
• dc.subject.keyword Variability
• dc.subject.keyword Diversity
• dc.subject.keyword Virus
• dc.subject.keyword Viral latency
• dc.subject.keyword Target enrichment
• dc.subject.keyword Inherited chromosomally integrated human
• dc.subject.keyword Phylogenetics
• dc.subject.keyword Selection
• dc.subject.keyword Viral load
• dc.subject.keyword 575
• dc.title Genetic diversity and geographic patterns of human herpesvirus 4 and 6
• dc.type info:eu-repo/semantics/doctoralThesis
• dc.type info:eu-repo/semantics/publishedVersion