Study of the DNA damage induced by Marek's disease virus and their involvement in the viral pathogenesis

Le virus de la maladie de Marek (MDV) est un alphaherpesvirus à l’origine du développement de lymphomes chez les volailles. A ce jour, l’origine du développement des tumeurs induites par le MDV est encore peu connue malgré l’identification de plusieurs oncoprotéines virales. Au vu de l’implication des dommages à l’ADN dans la pathogenèse de plusieurs virus notamment les herpesvirus, mon projet de thèse avait pour objectif de déterminer l’impact de l’apparition de lésions d’ADN sur le cycle viral du MDV. Nous avons montré que l’infection cytolytique de MDV s’accompagne d’une accumulation de lésions dans l’ADN cellulaire de lymphocytes et cellules fibroblastiques de poulet. La phase de latente de l’infection MDV n’affecte pas l’intégrité de l’ADN des lymphocytes alors que la réactivation du virus conduit à l’apparition de lésions d’ADN. De plus, en utilisant une approche originale in vivo, nous avons confirmé le rôle essentiel de la protéine virale VP22 dans l’induction de ces dommages. Nous avons pu établir que l’induction des dommages à l’ADN au cours de l’infection et/ou la réponse cellulaire engendrée sont non seulement favorables à la réplication du virus mais également que l’apparition de ces lésions est étroitement liée au pouvoir oncogène du MDV.Marek’s disease virus (MDV) is an alphaherpesvirus responsible of T lymphoma in chickens. Mechanisms leading to cellular transformation mediated by MDV are still incompletely understood. DNA damage and the associated cellular response participate actively in the life cycle of viruses, especially herpesviruses. Here, we aimed at deciphering the role of DNA damages in MDV pathogenesis. We show that MDV lytic infection leads to DNA lesions in lymphocytes and fibroblasts of chickens. Moreover, we demonstrated that MDV latently-infected lymphocytes exhibits undamaged DNA whereas MDV reactivation leads to an onset of DNA lesions. Also, using an original in vivo approach, we objectified the role of VP22 on DNA damages induction. Finally, we established that DNA damage and/or the associated DNA damage response are not only benefic to MDV replication but also that the DNA lesions onset might participate to MDV oncogenicity

Marek's disease virus induces DNA damage

National audienc

COVID-19 Vaccine Booster Hesitancy (VBH) and Its Drivers in Algeria: National Cross-Sectional Survey-Based Study

Due to the emergence of various highly contagious variants of SARS-CoV-2, vaccine boosters were adopted as a complementary strategy in different countries. This strategy has, however, posed another challenge for the national authorities to convince their population to receive the booster after the first challenge of COVID-19 primer dose vaccines. This study was conducted to determine COVID-19 vaccine booster acceptance and its associated factors in the general population in Algeria. Using social media platforms, an online self-administered questionnaire was distributed between 28 January and 5 March 2022 for all Algerian citizens who received COVID-19 vaccines. Overall, 787 respondents were included in this study. Among them, 51.6%, 25%, and 23.8% accepted, rejected, or were hesitant about the COVID-19 vaccine booster, respectively. However, only 13.2% declared receiving the booster dose. Additionally, while 58.2% of the respondents declared being relieved after primer vaccination, 11.4% among them declared that they regretted being vaccinated. The most common reasons for acceptance were experts’ recommendations (24.6%) and the belief that COVID-19 vaccine boosters were necessary and efficient, while rejection was mainly due to the belief that primer doses are sufficient (15.5%), or that vaccination in general is inefficient (8%). Males, older individuals, those with chronic comorbidities or a history of COVID-19 infection, non-healthcare workers, and those with low educational levels were associated with significantly higher odds for booster acceptance. Moreover, belief that booster doses were necessary and efficient, disagreeing with the notion that primer doses were not sufficient, experts’ recommendations, and the desire to travel abroad were significantly associated with higher odds of COVID-19 vaccine booster acceptance

COVID-19 Vaccine Booster Hesitancy (VBH) and Its Drivers in Algeria: National Cross-Sectional Survey-Based Study

Due to the emergence of various highly contagious variants of SARS-CoV-2, vaccine boosters were adopted as a complementary strategy in different countries. This strategy has, however, posed another challenge for the national authorities to convince their population to receive the booster after the first challenge of COVID-19 primer dose vaccines. This study was conducted to determine COVID-19 vaccine booster acceptance and its associated factors in the general population in Algeria. Using social media platforms, an online self-administered questionnaire was distributed between 28 January and 5 March 2022 for all Algerian citizens who received COVID-19 vaccines. Overall, 787 respondents were included in this study. Among them, 51.6%, 25%, and 23.8% accepted, rejected, or were hesitant about the COVID-19 vaccine booster, respectively. However, only 13.2% declared receiving the booster dose. Additionally, while 58.2% of the respondents declared being relieved after primer vaccination, 11.4% among them declared that they regretted being vaccinated. The most common reasons for acceptance were experts’ recommendations (24.6%) and the belief that COVID-19 vaccine boosters were necessary and efficient, while rejection was mainly due to the belief that primer doses are sufficient (15.5%), or that vaccination in general is inefficient (8%). Males, older individuals, those with chronic comorbidities or a history of COVID-19 infection, non-healthcare workers, and those with low educational levels were associated with significantly higher odds for booster acceptance. Moreover, belief that booster doses were necessary and efficient, disagreeing with the notion that primer doses were not sufficient, experts’ recommendations, and the desire to travel abroad were significantly associated with higher odds of COVID-19 vaccine booster acceptance

Étude des dommages à l’ADN au cours du cycle viral du virus de la Maladie de Marek

National audienc

Intención de recibir la vacuna contra la COVID-19 y sus factores predictivos asociados : estudio transversal entre el público general en Argelia

Background: Hesitancy towards COVID-19 vaccination and its rejection remains a major public health concern worldwide, especially in the Middle East and North African countries. The current study aimed to assess the intentions to get COVID-19 vaccines and its determinants among the general public in Algeria. Methods: A self-administered online survey was distributed during August-September 2021 using a convenience-based sampling approach. Data were collected anonymously and analyzed using IBM SPSS v22.0 software. Results: The study sample comprised a total of 656 participants, with 51.1% being in favor of COVID-19 vaccines while 18.5% and 30.5% were against or hesitant respectively. Only 38.6% among the study participants got vaccinated. Factors associated with higher odds of acceptance were: male sex, healthcare profession, the belief in natural origin of the pandemic and previous COVID-19 infection in family. The most common cited reasons for COVID-19 vaccine acceptance were the belief that vaccination is the only way to fight COVID-19 and the fear of getting infected by the virus; while the most common reasons of rejection were lack of trust in proper vaccine testing and fear of side effects. Conclusion: The overall level of COVID-19 vaccine acceptance in this study was below the levels required to achieve population immunity. Besides certain socio-demographic characteristics, the determinants of COVID-19 vaccine rejection included the embrace of conspiratorial ideas regarding the virus and its vaccination. This should be considered in implementation of interventional measures aiming to promote COVID-19 vaccination in the country

Implication of cellular DNA damage triggered by Marek's disease virus infection in viral replication and pathogenesis

National audienc

Rôle des dommages à l’ADN dans le cycle viral du virus de la Maladie de Marek

National audienceLe virus de la maladie de Marek (MDV) est un herpesvirus à l’origine du développement de lymphomes chez les volailles. A ce jour, les mécanismes moléculaires conduisant à la tumorigenèse viro-induite sont encore méconnus malgré l’identification d’oncogènes viraux. Récemment nous avons montré que l’infection par le MDV induit une dérégulation du cycle cellulaire se traduisant par un arrêt prolifératif en phase-S et que la protéine virale VP22 jouerait un rôle majeur dans ce processus. La surexpression de VP22 entraine un arrêt drastique intra-S mais elle engendre également de nombreuses cassures double-brins (CDB) dans l’ADN. Aussi, au vu de l’implication des dommages à l’ADN dans les processus néoplasiques, nous avons initié un projet visant à préciser l’impact de l’infection par le MDV sur l’intégrité génomique. Nous avons ainsi pu mettre en évidence in vivo et in vitro que la réplication du MDV est associée à une accumulation de cassures (double-brin) dans l’ADN des cellules infectés et que l’induction de ces dommages et/ou la réponse cellulaire engendrée seraient favorables à la réplication du virus. De plus, l’apparition de ces lésions serait également étroitement liée au pouvoir oncogène du MDV. En effet, les lymphocytes de poulets infectés par un virus atténué présentent un taux de dommage significativement plus faible que celui détecté à partir de lymphocytes de poulets infectés par une souche oncogène. Par conséquent, les lésions générées dans l’ADN cellulaire lors de l’infection par le MDV pourraient non seulement favoriser la réplication du virus, mais également participer à l’induction d’une instabilité génomique à l’origine de la tumorigenèse viro-induite

Étude des dommages à l'ADN au cours du cyle viral du virus de la maladie de Marek

National audienc