O presente estudo listou e analisou a composição e a estrutura da comunidade de saturnídeos atraídos por luz da Estação Biológica de Boraceia (EBB), Salesóplis, São Paulo, Brasil. A EBB pertence ao Museu de Zoologia da Universidade de São Paulo (MZUSP) e compreende uma área de 96 ha, por sua vez localizada dentro do maior remanescente brasileiro de Mata Atlântica da atualidade. A fauna de Saturniidae foi levantada através de exemplares da coleção de Lepidoptera do MZUSP, sendo estes dados complementados com 13 meses de coletas recentes, entre 2012 e 2013, quando foram realizadas coletas noturnas de 12 horas, por quatro noites em cada mês. Adicionalmente, foi produzida uma lista de 114 espécies de Saturniidae coletados no bioma Mata Atlântica, para muitas das quais foram gerados registros fotográficos in situ e de exemplares montados. Os dados oriundos deste levantamento foram comparados com outros estudos sobre Saturniidae realizados no Brasil e demonstraram número elevado de espécies para EBB (119 espécies) quando comparado aos dados disponíveis de outros levantamentos, como os de Saturniidae do Rio Grande do Sul, do Paraná e do bioma (ou ecótono) Cerrado. Os dados das coletas recentes (2012-2013) foram comparados com a assembleia destes lepidópteros amostrada em 25 meses consecutivos durante os anos de 1948 a 1950. Esta comparação demonstrou que a riqueza e a uniformidade das espécies registradas recentemente (2012-2013) é significativamente próxima daquela registrada no período histórico (1948-1950). Alguns exemplares representaram novos registros de espécies para EBB, e algumas espécies foram coletadas exclusivamente em algum momento de todo o período histórico. A área de coleta demonstrou grande densidade de espécies do gênero Hylesia Hübner, 1920 com pelo menos 15 espécies (sendo destas 3 morfoespécies) coletadas em 1.158 exemplares. Estes resultados asseguram a importância do remanescente de Mata Atlântica da Serra do Mar para manutenção de espécies de Saturniidae e ainda, demonstram a significância da EBB para estudos faunísticos de insetos da Mata Atlântica. Algumas avaliações sobre as distribuições sazonal e circadiana dos exemplares coletados em 2012-2013 apontaram padrões que poderão ser utilizados para testar hipóteses de comportamento e biologia das espécies. As espécies apresentaram tanto distribuição restrita ao longo do ano, quanto foram mais amplamente distribuídas. Da mesma forma algumas espécies apresentaram altos picos de abundâncias em períodos restritos da noite, enquanto outras ocorreram em distintos horários. A avaliação da alternância de espécies ao longo do ano e ao longo da noite indicou que há alta alternância de espécies para ambos os ciclos, ressaltando a importância de um levantamento que se ocupe com coletas durante todos os meses do ano e durante todo o período noturno. Demonstrou ainda, que a flutuação de abundância das espécies agrupadas em cada uma das cinco subfamílias representadas nas amostras, seguem padrões tanto semelhantes, quanto contrastantes. / This study evaluated and summarized the composition and structure of the saturniid community attracted to light trapping in a remnant of Atlantic Rainforest of the Boraceia Biological Station (EBB), Salesópolis, São Paulo, Brazil. The EBB belongs to Zoological Museum of University of São Paulo (MZUSP) and comprises a 96 ha area located inside the largest Brazilina remananent of the Atlantica Rain Forest. The Saturniidae fauna of this reserve was inventoried based on the specimens deposited at the MZUSP, and it was complemented with 13 months of recently field samplings between 2012 and 2013. Complementary field sampling was based on nocturnal collections of 12 hours along four nights on each of the 13 months. As a result we listed 114 species of the family Saturniidae. Many species were photographed in situ, for illustration of the dorsal and ventral habitus of each species we used the pinned specimens of the collection. Comparisons with other inventories of Saturniidae conducted in different Brazilian localities were performed and demonstrated an elevated number of species in EBB when compared to the data available from other inverntories, from Rio Grande do Sul state, Paraná state and the Savana bioma. Recent field samplings (2012-2013) were compared with the assemblage of saturniids from 25 consecutive months between 1948 and 1950. This comparison demonstrated that the richness and the uniformity of the species recentelly registered (2012-2013) is similar to that from the historical period (1948-1950). Few specimens constituted new record for EBB and other few were sampled exclusively on the whole range of the historical period. The studied area indicated high density of species of Hyleisa Hübner, 1920 with at least 15 species (with three morphospecies) collected, distributed in 1.158 specimens. The results stress the importance of the Serra do Mar Atlatic forest remanent to the conservation of the species of Saturniidae and yet, demonstrate the importance of EBB for the study of insects from the Atlantic Rain Forest. The analysis related to the seasonality and circadian pattern of the recently collected specimens (2012-2013) can be further used to test hypothesis of behavior and biology of the species. The abundance of species showed distinct fluctuation along the year, while some had concentrated distribution, others were broadly sampled along several months. Similarly, some species presented high pics of abundance on restricted periods during the night, while other speces were sampled in several distinct periods. The evaluation of the interchange of species during the year and during the night indicated hight interchanging of species for both cicles, sazonal and cyrcadina, stressing the importance of inventories of Saturniidae with effort along the entire year and along the hole night period. The same evaluation also demonstrated that the fluctuation of the abundance of species grouped by subfamilies follow similar and contrasting patters depending on the subfamilies that are being compaired.

The circadian cycle, although seasonally adjusted, consists of two phases: a nocturnal period of darkness and a diurnal period of light. Many parameters of human physiology display either a nocturnal or diurnal peak as seen in athletic performance, immune, endocrine, physiology and cognitive function, respectively. The studies included in this thesis focused on the diurnal (morning or AM versus evening or PM) effect of high-intensity self-paced exercise on physiological and immunological measures and the influence of individual preference for activity or chronotype on these responses. Self-paced time-trials were completed in an environmental chamber (6°C) in the AM and PM and displayed a similar effect on physiological and biological parameters. Performance times were non-statistically quicker (P > 0.05) at PM. Physiological parameters heart rate, rate of perceived exertion, lung function and self-paced treadmill speed were not found to be statistically different at AM or PM trial (p > 0.05). Core body temperature (CBT), was significantly higher (p0.05). CD8+ T-lymphocyte cell-surface markers for naïve/senescence and differentiation (CD27CD45RA and CD27CD28) reported no diurnal difference between AM and PM exercise in experienced and experienced/recreational distance runners respectively (P > 0.05). However, a higher percentage of highly differentiated phenotypes were found in the recreationally active population. Neutrophils displayed a pronounced elevation in response to PM exercise with the mechanism driving this response unclear at this time. Cortisol concentration displayed less inflammatory responses in the morning compared to the evening with higher values pre, post and one-hour post AM trials. Chronotype showed no effect on physiology or biology at rest or in response to exercise. Chapter 4 presents data from a study that investigated diurnal physiology and immune response to high-intensity exercise in highly-trained men. Recreational and experienced endurance male runners at differing diurnal time-points were investigated in Chapter 5, while individual chronotype differences and circadian phase responses were explored in Chapter 6.In summary, it is concluded from this work that there was a lack of evidence showing a diurnal effect on running performance and subsequent immune response. Elevated circulating immune counts prior to exercise, irrespective of diurnal phase, appear to govern exercise-induced responses. The effect of high intensity exercise is subject to three distinct variables: the fitness status and experience of the individual completing the exercise, the time of day at which the exercise is undertaken, and the phase response of exercise at that point of the circadian cycle. No diurnal phase mediated a divergent effect on variables examined was observed at 09.00hrs and 17.00hrs. These time-points should be considered not sufficiently dissimilar to elucidate diurnal variation in trained and healthy males.

O presente estudo listou e analisou a composição e a estrutura da comunidade de saturnídeos atraídos por luz da Estação Biológica de Boraceia (EBB), Salesóplis, São Paulo, Brasil. A EBB pertence ao Museu de Zoologia da Universidade de São Paulo (MZUSP) e compreende uma área de 96 ha, por sua vez localizada dentro do maior remanescente brasileiro de Mata Atlântica da atualidade. A fauna de Saturniidae foi levantada através de exemplares da coleção de Lepidoptera do MZUSP, sendo estes dados complementados com 13 meses de coletas recentes, entre 2012 e 2013, quando foram realizadas coletas noturnas de 12 horas, por quatro noites em cada mês. Adicionalmente, foi produzida uma lista de 114 espécies de Saturniidae coletados no bioma Mata Atlântica, para muitas das quais foram gerados registros fotográficos in situ e de exemplares montados. Os dados oriundos deste levantamento foram comparados com outros estudos sobre Saturniidae realizados no Brasil e demonstraram número elevado de espécies para EBB (119 espécies) quando comparado aos dados disponíveis de outros levantamentos, como os de Saturniidae do Rio Grande do Sul, do Paraná e do bioma (ou ecótono) Cerrado. Os dados das coletas recentes (2012-2013) foram comparados com a assembleia destes lepidópteros amostrada em 25 meses consecutivos durante os anos de 1948 a 1950. Esta comparação demonstrou que a riqueza e a uniformidade das espécies registradas recentemente (2012-2013) é significativamente próxima daquela registrada no período histórico (1948-1950). Alguns exemplares representaram novos registros de espécies para EBB, e algumas espécies foram coletadas exclusivamente em algum momento de todo o período histórico. A área de coleta demonstrou grande densidade de espécies do gênero Hylesia Hübner, 1920 com pelo menos 15 espécies (sendo destas 3 morfoespécies) coletadas em 1.158 exemplares. Estes resultados asseguram a importância do remanescente de Mata Atlântica da Serra do Mar para manutenção de espécies de Saturniidae e ainda, demonstram a significância da EBB para estudos faunísticos de insetos da Mata Atlântica. Algumas avaliações sobre as distribuições sazonal e circadiana dos exemplares coletados em 2012-2013 apontaram padrões que poderão ser utilizados para testar hipóteses de comportamento e biologia das espécies. As espécies apresentaram tanto distribuição restrita ao longo do ano, quanto foram mais amplamente distribuídas. Da mesma forma algumas espécies apresentaram altos picos de abundâncias em períodos restritos da noite, enquanto outras ocorreram em distintos horários. A avaliação da alternância de espécies ao longo do ano e ao longo da noite indicou que há alta alternância de espécies para ambos os ciclos, ressaltando a importância de um levantamento que se ocupe com coletas durante todos os meses do ano e durante todo o período noturno. Demonstrou ainda, que a flutuação de abundância das espécies agrupadas em cada uma das cinco subfamílias representadas nas amostras, seguem padrões tanto semelhantes, quanto contrastantes. / This study evaluated and summarized the composition and structure of the saturniid community attracted to light trapping in a remnant of Atlantic Rainforest of the Boraceia Biological Station (EBB), Salesópolis, São Paulo, Brazil. The EBB belongs to Zoological Museum of University of São Paulo (MZUSP) and comprises a 96 ha area located inside the largest Brazilina remananent of the Atlantica Rain Forest. The Saturniidae fauna of this reserve was inventoried based on the specimens deposited at the MZUSP, and it was complemented with 13 months of recently field samplings between 2012 and 2013. Complementary field sampling was based on nocturnal collections of 12 hours along four nights on each of the 13 months. As a result we listed 114 species of the family Saturniidae. Many species were photographed in situ, for illustration of the dorsal and ventral habitus of each species we used the pinned specimens of the collection. Comparisons with other inventories of Saturniidae conducted in different Brazilian localities were performed and demonstrated an elevated number of species in EBB when compared to the data available from other inverntories, from Rio Grande do Sul state, Paraná state and the Savana bioma. Recent field samplings (2012-2013) were compared with the assemblage of saturniids from 25 consecutive months between 1948 and 1950. This comparison demonstrated that the richness and the uniformity of the species recentelly registered (2012-2013) is similar to that from the historical period (1948-1950). Few specimens constituted new record for EBB and other few were sampled exclusively on the whole range of the historical period. The studied area indicated high density of species of Hyleisa Hübner, 1920 with at least 15 species (with three morphospecies) collected, distributed in 1.158 specimens. The results stress the importance of the Serra do Mar Atlatic forest remanent to the conservation of the species of Saturniidae and yet, demonstrate the importance of EBB for the study of insects from the Atlantic Rain Forest. The analysis related to the seasonality and circadian pattern of the recently collected specimens (2012-2013) can be further used to test hypothesis of behavior and biology of the species. The abundance of species showed distinct fluctuation along the year, while some had concentrated distribution, others were broadly sampled along several months. Similarly, some species presented high pics of abundance on restricted periods during the night, while other speces were sampled in several distinct periods. The evaluation of the interchange of species during the year and during the night indicated hight interchanging of species for both cicles, sazonal and cyrcadina, stressing the importance of inventories of Saturniidae with effort along the entire year and along the hole night period. The same evaluation also demonstrated that the fluctuation of the abundance of species grouped by subfamilies follow similar and contrasting patters depending on the subfamilies that are being compaired.

There is a noticeable difference in the debate regarding adolescents’ sleep patterns between the biological clock and society’s clock when we talk about adolescents. Sleep scientists or somnologists, are alarming as more evidence reach the surface that young people are not getting the recommended sleep that is required to perform academically well. Not only are there direct connections between sleep deficit and academic performance, but sleep deficit also takes a critical toll upon their physical and mental health. The problem is that adolescents’ circadian cycle is postponed with a few hours compared to children and adults. This results in a major sleep deficit when adolescents must adjust to societal rhythms and habits – a clock they are not programmed biologically to follow. Adolescents must attend to school in the early morning, when in reality their needs point to that school times in fact should start around 10:00. Society’s view has traditionally been that teenagers are lazy but in fact evidence does prove that it may not be the case. The following essay will therefore serve as an informative update to what has been stated by somnologists and raise awareness regarding adolescents and what happens when they are exposed to a chronic sleep deficit put on them by society.

O complexo de espécies crípticas de Anastrepha fraterculus compreende oito morfotipos dos quais três ocorrem no Brasil. Anastrepha sp.1 aff. fraterculus é o morfotipo Brasil-1 e é uma espécie de ampla distribuição no planalto sudeste/sul do Brasil e no norte da Argentina. O comportamento reprodutivo dessa espécie é complexo, envolvendo uma série de movimentos desempenhados pelos machos para atrair as fêmeas para acasalamento, e ocorre, preferencialmente, nas primeiras horas do dia. Dois genes, period e fruitless, entre outros, são conhecidos por participar do controle do comportamento reprodutivo de vários organismos, incluindo algumas espécies de moscas-das-frutas. O presente trabalho buscou informações sobre a atuação desses genes no comportamento reprodutivo de A. sp.1, utilizando o silenciamento transitório desses genes pela metodologia de RNA interferente. Foram, primeiramente, desenhados iniciadores específicos para amplificar fragmentos do DNA genômico desses genes, sendo demonstrado que apresentaram uma similaridade entre 97 a 99% com os genes equivalentes de outras espécies de Anastrepha. A seguir, após padronização e adaptação de protocolos, foram sintetizados os RNA de dupla-fita (dsRNA) dos dois genes, que foram, então, utilizados nos experimentos de silenciamento. Análises, para verificação se os genes foram realmente silenciados foram feitas a partir a injeção dos dsRNAfru e/ou dsRNAper no abdomên de machos sexualmente maduros, tendo sido demonstrado que os genes estavam silenciados ao máximo, sete a oito dias após a injeção. Interferências no comportamento de machos sexualmente maduros, com um ou outro gene silenciado, foram avaliados por testes relacionados com dois parâmetros do comportamento reprodutivo: alterações nas atividades gerais (qualquer tipo de movimentação dos insetos) dos machos durante o ciclo circadiano (dia/noite) e mais especificamente, a atividade relacionada ao comportamento reprodutivo. Ao injetar dsRNAfru em machos adultos de A. sp.1 foi observado que não houve alteração significativa nas suas atividades gerais. Porém, foi observado que houve uma diminuição significativa no número de machos que realizavam atividades reprodutivas, sugerindo que o silenciamento de fruitless no macho adulto altera o funcionamento normal do comportamento sexual masculino. Em contrapartida, ao injetar dsRNAper em machos adultos de A. sp.1 não foi observada alteração significativa tanto nas suas atividades reprodutivas quanto nas atividades gerais. O silenciamento dos genes aparentemente não afeta a produção de espermatozóides. Apesar de controverso, esses dados corroboram com o que foi observado em D. melanogaster, em que o mutante nulo per04 não apresenta alteração significativa nos seus comportamentos em relação aos machos selavagens em um regime cíclico Dia/Noite. Dessa forma, análises adicionais serão necessárias com o objetivo de elucidar as implicações desses dois genes no comportamento locomotor e reprodutivo de Anastrepha sp.1 aff. fraterculus. / The complex of cryptic species Anastrepha fraterculus comprises eight morphotypes three of which occur in Brazil. Anastrepha sp.1 aff. fraterculus correspond to the morphotype Brazil-1 and is a species of wide distribution in the southeast/south plateau of Brazil and in north of Argentina. The reproductive behavior of this species is complex, involving a series of movements performed by males to attract females for mating, and occurs in the early hours of the day. Two genes, period and fruitless, among others, are known to participate in the control of reproductive behavior of various organisms, including some species of fruit flies. The present work aimed to get information about the presumable role of these genes in the reproductive behavior of A. sp.1, using transient silencing of these genes by interfering RNA methodology. Specific primers were first designed to amplify fragments of the genomic DNA of these genes, showing they have a similarity between 97 to 99% with the equivalent genes of other Anastrepha species. After standardization and adaptation of protocols, the double-stranded RNA (dsRNA) of the two genes were synthesized, and used in the silencing experiments. Tests to verify that the genes were actually silenced, were made after injection of the dsRNAfru and/or dsRNAper into the abdomens of sexually mature males. These tests showed that the genes were silenced to the maximum, seven to eight days after the injection. Interferences in the behavior of sexually mature males with one or other silenced gene were evaluated by tests related to two parameters of reproductive behavior: changes in the general activities (any type of movement of insects) of males during the circadian cycle (day/night) and more specifically, activity related to reproductive behavior. Injection of dsRNAfru in adult males of A. sp.1 showed that they did not cause significant alterations in general activities, but it was observed that they cause a significant decrease in the number of males that performed reproductive activities, suggesting that silencing of fruitless. alters the normal functioning of male sexual behavior. In contrast, when injecting dsRNAper. in adult males of A. sp.1, no significant alteration was observed neither in their reproductive activities nor in their general activities. Moreover, silencing of the genes seems not to affect the production of spermatozoa. Although controversial, the data are in line with observations in D. melanogaster, in which the null mutant per04 did not present significant alterations in behaviors relatives to the control males in a Day/Night cyclic regime. Thus, additional analyzes will be needed to elucidate the participation of the two genes in the coordination of behaviors in Anastrepha sp.1 aff fraterculus.

O complexo de espécies crípticas de Anastrepha fraterculus compreende oito morfotipos dos quais três ocorrem no Brasil. Anastrepha sp.1 aff. fraterculus é o morfotipo Brasil-1 e é uma espécie de ampla distribuição no planalto sudeste/sul do Brasil e no norte da Argentina. O comportamento reprodutivo dessa espécie é complexo, envolvendo uma série de movimentos desempenhados pelos machos para atrair as fêmeas para acasalamento, e ocorre, preferencialmente, nas primeiras horas do dia. Dois genes, period e fruitless, entre outros, são conhecidos por participar do controle do comportamento reprodutivo de vários organismos, incluindo algumas espécies de moscas-das-frutas. O presente trabalho buscou informações sobre a atuação desses genes no comportamento reprodutivo de A. sp.1, utilizando o silenciamento transitório desses genes pela metodologia de RNA interferente. Foram, primeiramente, desenhados iniciadores específicos para amplificar fragmentos do DNA genômico desses genes, sendo demonstrado que apresentaram uma similaridade entre 97 a 99% com os genes equivalentes de outras espécies de Anastrepha. A seguir, após padronização e adaptação de protocolos, foram sintetizados os RNA de dupla-fita (dsRNA) dos dois genes, que foram, então, utilizados nos experimentos de silenciamento. Análises, para verificação se os genes foram realmente silenciados foram feitas a partir a injeção dos dsRNAfru e/ou dsRNAper no abdomên de machos sexualmente maduros, tendo sido demonstrado que os genes estavam silenciados ao máximo, sete a oito dias após a injeção. Interferências no comportamento de machos sexualmente maduros, com um ou outro gene silenciado, foram avaliados por testes relacionados com dois parâmetros do comportamento reprodutivo: alterações nas atividades gerais (qualquer tipo de movimentação dos insetos) dos machos durante o ciclo circadiano (dia/noite) e mais especificamente, a atividade relacionada ao comportamento reprodutivo. Ao injetar dsRNAfru em machos adultos de A. sp.1 foi observado que não houve alteração significativa nas suas atividades gerais. Porém, foi observado que houve uma diminuição significativa no número de machos que realizavam atividades reprodutivas, sugerindo que o silenciamento de fruitless no macho adulto altera o funcionamento normal do comportamento sexual masculino. Em contrapartida, ao injetar dsRNAper em machos adultos de A. sp.1 não foi observada alteração significativa tanto nas suas atividades reprodutivas quanto nas atividades gerais. O silenciamento dos genes aparentemente não afeta a produção de espermatozóides. Apesar de controverso, esses dados corroboram com o que foi observado em D. melanogaster, em que o mutante nulo per04 não apresenta alteração significativa nos seus comportamentos em relação aos machos selavagens em um regime cíclico Dia/Noite. Dessa forma, análises adicionais serão necessárias com o objetivo de elucidar as implicações desses dois genes no comportamento locomotor e reprodutivo de Anastrepha sp.1 aff. fraterculus. / The complex of cryptic species Anastrepha fraterculus comprises eight morphotypes three of which occur in Brazil. Anastrepha sp.1 aff. fraterculus correspond to the morphotype Brazil-1 and is a species of wide distribution in the southeast/south plateau of Brazil and in north of Argentina. The reproductive behavior of this species is complex, involving a series of movements performed by males to attract females for mating, and occurs in the early hours of the day. Two genes, period and fruitless, among others, are known to participate in the control of reproductive behavior of various organisms, including some species of fruit flies. The present work aimed to get information about the presumable role of these genes in the reproductive behavior of A. sp.1, using transient silencing of these genes by interfering RNA methodology. Specific primers were first designed to amplify fragments of the genomic DNA of these genes, showing they have a similarity between 97 to 99% with the equivalent genes of other Anastrepha species. After standardization and adaptation of protocols, the double-stranded RNA (dsRNA) of the two genes were synthesized, and used in the silencing experiments. Tests to verify that the genes were actually silenced, were made after injection of the dsRNAfru and/or dsRNAper into the abdomens of sexually mature males. These tests showed that the genes were silenced to the maximum, seven to eight days after the injection. Interferences in the behavior of sexually mature males with one or other silenced gene were evaluated by tests related to two parameters of reproductive behavior: changes in the general activities (any type of movement of insects) of males during the circadian cycle (day/night) and more specifically, activity related to reproductive behavior. Injection of dsRNAfru in adult males of A. sp.1 showed that they did not cause significant alterations in general activities, but it was observed that they cause a significant decrease in the number of males that performed reproductive activities, suggesting that silencing of fruitless. alters the normal functioning of male sexual behavior. In contrast, when injecting dsRNAper. in adult males of A. sp.1, no significant alteration was observed neither in their reproductive activities nor in their general activities. Moreover, silencing of the genes seems not to affect the production of spermatozoa. Although controversial, the data are in line with observations in D. melanogaster, in which the null mutant per04 did not present significant alterations in behaviors relatives to the control males in a Day/Night cyclic regime. Thus, additional analyzes will be needed to elucidate the participation of the two genes in the coordination of behaviors in Anastrepha sp.1 aff fraterculus.

L'infection au virus de l'hépatite B (VHB) est étroitement liée au métabolisme énergétique hépatique. La réplication du virus est contrôlée en principal par des facteurs de transcription et récepteurs nucléaires tels que PPARa, HNF4a et Foxül, impliqués dans ce métabolisme. Ainsi, la réplication du virus est augmentée par la privation de nutriments et le stress énergétique en modèles cellulaires, et par le jeûne, en modèles murins. PGC-la, un régulateur majeur de la réponse métabolique adaptative au jeûne, est impliqué dans l'augmentation de la transcription du VHB par son interaction avec plusieurs facteurs de transcription. Il est connu que le récepteur des acides biliaires, FXRa, qui est capable d'activer le promoteur de Core du VHB, est co-activaté par PGC-la. Un autre acteur important dans l'adaptation métabolique à la privation d'énergie est la protéine déacétylase SIRTl. Lorsqu'il est activé, SIRTl hépatique est capable de désacétyler et activer autant PGC-la que FXRa. Ces données nous ont amenés à émettre l'hypothèse que SIRTl pourrait coopérer avec FXRa et PGC-la pour augmenter la transcription du VHB. Dans un premier travail, nous avons donc étudié le rôle de la coopération de ces trois facteurs métaboliques dans la réplication du virus. Ça nous a permis de décrire un nouveau réseau métabolique, composé de FXRa, PGC-la et SIRTl, qui régule l'activité transcriptionnelle du VHB. Nous avons montré que SIRTl augmente l'activité du promoteur de Core par l'intermède d'autre facteurs, parmi lesquels, FXRa. Nous avons en outre observé que la fonction de déacétylase de SIRTl était nécessaire pour l'amplification de l'effet de FXRa sur VHB promoteur de Core. Une autre cible de SIRTl, connue pour son activité co-activatrice sur FXRa, est PGC-la. Grâce à une série d'expériences de surexpression et suppression, nous avons montré que non seulement la co-activation de FXRa par PGC-la est potentialisée par SIRTl, mais la présence de PGC-la est nécessaire pour l'effet de SIRTl sur l'activation du promoteur de Core VHB induite par FXRa. Ces données suggèrent que FXRa, PGC-la et SIRTl coopèrent dans la modulation de l'activité transcriptionnelle du promoteur de Core. Nous avons ensuite confirmé nos observations initiales et avons montré que l'activation de l'axe SIRTl/PGC-la/FXRa induit la transcription de l'ARN de VHB dans des lignées cellulaires d'origine hépatique et non-hépatique. Ces résultats renforcent l'idée que la réplication du VHB peut être modulée en fonction de l'état nutritionnel. Les rapports des études précédentes menées in vitro et sur des modèles animaux suggèrent que la transcription du VHB est contrôlée de la même manière que les gènes de la néoglucogenèse. Notre hypothèse a été que chez l'homme, la réplication du VHB montrerait des fluctuations diurnes, selon les périodes de la journée de jeûne et de réalimentation. Le but de la deuxième étude a été donc de déterminer si la charge viral du VHB plasmatique montre des variations importantes tout au long du nichthemeron chez les patients chroniquement infectés par VHB, avec une réplication virale active [etc...] / Hepatitis B virus (HBV) infection is tightly linked with hepatic fuel metabolism. HBV replication depends on the activity of several liver-enriched nuclear receptors and transcription factors, such as PPARa, HNF4a, and Fox01, involved in the metabolic adaptive response to fasting. In the first part of our work, we identified a metabolic subnetwork that enhances the activity of HBV core promoter. FXRa (NR1H4), PPAR gamma coactivator 1a and SIRT1, the members of this regulatory axis, cooperate to increase HBV transcription. The three molecules are themselves key factors of liver metabolism, linking HBV replication to complex metabolic cues, such as energy status and nutrient availability during the fasting-refeeding cycles. We then observed the existence of a circadian cycle of HBV replication in humans, underlining the role of nutrient availability in the modulation of HBV replication, previously predicted by experimental models. The second part of the work focused on the plasma cell-free nucleic acids as potential biomarkers in chronic viral hepatitis. Due to the multiple links between HBV replication and cellular factors involved in fuel metabolism, we hypothesized that plasma mRNAs corresponding to these factors may constitute potential biomarkers for chronic hepatitis B. We successfully detected more than 30 plasma mRNA sequences corresponding to enzymes, transporters, nuclear receptors and transcription factors involved in fatty acids synthesis and oxidation, cholesterol synthesis, transport and excretion, and energy sensing and expenditure. The circadian variation and the multiple correlations in the expression patterns of these plasma transcripts are similar to those previously described in cells both in vitro and in vivo. This suggests that cell- free mRNAs may provide a "virtual biopsy" of the transcriptional status of the organism. Moreover, we found significant differences in the plasma mRNA profiles of HBV carriers compared with healthy controls, similar to those found in experimental models of infection, suggesting that these transcripts may also serve as biomarkers of liver disease. Further research is warranted to shed new light on the complex relationship between HBV life cycle and host lipid-carbohydrate-fuel metabolism and may lead to the identification of both actionable targets in antiviral therapy, and putative biomarkers in chronic hepatitis B