Bovine Leukemia Virus (BLV) latency is a viral strategy used to escape from the host immune system and contribute to tumor development. However, the recent discovery of a highly expressed miRNA cluster has suggested that BLV latency is partially true. In our PhD thesis, we studied the epigenetic and transcriptional regulations of this RNA polymerase III (RNAPIII)- dependent miRNA cluster and of a newly discovered RNA polymerase II (RNAPII)-dependent promoter (which drives an active antisense transcription). Moreover, our data suggested a putative collision phenomenon between RNAPII and RNAPIII convergent transcriptions. In the second part of our PhD thesis, we therefore provided new insights into this complex transcriptional network. In the third part of this work, we demonstrated the recruitment of CTCF, a multi-functional transcriptional regulator, along the BLV genome and provided data explaining its putative functions in BLV transcriptional and epigenetic regulations but also in viral-host genome long-range interactions. In conclusion, our PhD thesis provides a better understanding of the transcriptional network regulating BLV gene expression and new ideas to study BLV-induced leukemia development. La latence virale, principale caractéristique de l’infection par le virus de la leucémie bovine (BLV), permet au virus d’échapper au système immunitaire de l’hôte et contribue au développement tumoral. Cependant, la récente découverte d’une région codant pour des miRNAs viraux et activement transcrite par l’ARN polymérase III (RNAPIII), suggère que la latence virale n’est que partiellement vraie. Dans cette thèse, nous avons étudié les régulations transcriptionnelle et épigénétique du promoteur RNAPIII-dépendant contrôlant l’expression des miRNAs du BLV, ainsi que celles d’un nouveau promoteur ARN polymérase II (RNAPII)-dépendant, découvert au cours de notre travail de thèse. Suite à nos données, suggérant de l’interférence transcriptionnelle, nous avons ensuite étudié le fonctionnement de ce réseau transcriptionnel complexe composé de trois promoteurs distincts régulant l’expression du BLV. Finalement, nous avons démontré le recrutement de CTCF, un régulateur transcriptionnel multifonctionnel, le long du génome du BLV et nos résultats suggèrent des potentielles fonctions de CTCF dans les régulations transcriptionnelle et épigénétique du BLV, mais également dans des interactions longue-distances entre le virus et le génome de la cellule hôte. En conclusion, notre thèse de doctorat apporte une meilleure compréhension du réseau transcriptionnel régulant l’expression génique du BLV et offre de nouvelles pistes pour l’étude du développement tumoral induit par le BLV. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

What explains the geographic distribution of pathogens? Better understanding and characterising disease patterns will help scientists to identify areas likely to host future epidemics and epizootics and to prioritise surveillance and intervention. However, the use of disease surveillance data to assess the risk of transmission and generate risk maps raises conceptual and methodological issues. Indeed, pathogens and more particularly viruses aren't ”species” like others that live in the open environment and must be studied with methods and concepts of their own. Avian influenza (AI), a disease caused by a virus infecting bird populations, has been selected to study these issues. AI has a major economic impact on the poultry industry in many countries, raises concerns of livelihood in low and middle-income countries, and represents a major concern for human health. The aim of this PhD thesis was to improve the knowledge on the spatial epidemiology of AI in different settings and conditions (i). For this, recent epizootics caused by the subtypes A (H5N1) and A (H7N9) were selected as case studies. First, highly pathogenic subtypes of the A (H5N1) virus have been studied in poultry farms (ducks and chickens) at different spatial scales: at the continental scale and the regional scale in the Mekong (Cambodia, Laos, Vietnam, Thailand) and the Nile Delta in Egypt. All these cases occurred between 2003, the date on which the virus starts to spread outside China, and 2015; the HPAI A (H5N1) subtypes are still reported today in many countries. Human infections caused by the A (H7N9) virus in China from March 2013 to 2017 were also studied. Studied different AI subtypes at different spatial scales within different host species also allowed to develop a conceptual model of AI transmission and to discuss the issue of the transferability of results in epidemiology (ii). Lastly, this PhD thesis leads to a discussion about the transfer of methods and concepts from ecology to spatial epidemiology, with a particular emphasis on their possible limitations (iii). / Doctorat en Sciences agronomiques et ingénierie biologique / info:eu-repo/semantics/nonPublished