PhD defense of Daed EL SAFADI on December 19th 2024

Dead EL SAFADI will defend her PhD thesis on December 19, 2024, at 13:00 p.m. (Reunion time), in the CHARPAK amphitheater at the University of Reunion Island, Moufia, Saint-Denis.

Study of Host-Pathogen Interactions During Zika and Dengue Virus Infections 

Abstract: Reunion Island provides an ideal tropical environment for the proliferation of Aedes mosquitoes, which are the primary vectors of arboviruses such as Dengue, Chikungunya, and Zika viruses. Despite vector control measures, arbovirus outbreaks remain a significant public health concern due to the absence of proven treatments and efficient vaccines. A dengue epidemic that began in 2018 has resulted in approximately 72,000 cases and 52 deaths to date, revealing severe ocular manifestations that have been inadequately documented thus far. Infections by Dengue and Zika viruses, both members of the Flaviviridae family, are often asymptomatic. When symptoms do manifest, they range from flu-like symptoms to severe forms, such as hemorrhagic fever for dengue and neurological disorders and congenital syndromes for Zika. Both viruses have been described as capable of causing retinal damage by affecting the blood-retinal barrier. During my PhD research, I investigated the cellular defense mechanisms of the host that may contribute to the pathophysiology during infections with Dengue and Zika viruses. I focused on pathways such as endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), apoptosis, metabolic reprogramming, and extracellular vesicle (EV)-mediated communication. My research highlighted the regulation of the UPR-apoptosis axis by Zika virus through the inhibition of the CHOP protein, and the exploitation of EVs by both viruses to vectorize their non-structural protein NS1. I also explored the antiviral potential of adipoRon, an agonist of AdipoR receptors that activates the AMPK/PPARα/CPT1 pathway associated with mitochondrial oxidative metabolism, thereby contributing to demonstrating the impact of metabolism on infection. Additionally, I characterized the infection of retinal pigment epithelial (RPE) cells by both viruses, which are critical components of the blood-retinal barrier. Overall, my work emphasizes the critical interactions between the host and the virus, paving the way for new promising therapeutic strategies to combat flavivirus infections.

Members of the jury
Dr. Pascale KREJBICH-TROTOT | Directrice de thèse
Pr. Joelle SOBCZAK-THEPOT | Rapportrice
Pr. Catherine CETRE-SOSSAH | Rapportrice
Dr. Dani OSMAN | Examinateur
Pr. Sébastien LHOMME | Examinateur