Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses

• Autor(a) principal: Ferreira, Rui Filipe Tavares
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/35967
• topic: Viruses; Reroxisomes; Antiviral immunity; MAVS; STING

Peroxisomes are dynamic intracellular organelles, essential for diverse cellular functions, and implicated in different pathological processes. This organelle has also been described as an important signalling platform for the cellular antiviral response. Upon virus entry, cytosolic receptors, such as RIG-I or cGAS, sense the viral nucleic acids, activating specific signaling pathways dependent, respectively, on the protein adaptors MAVS (at the mitochondria and peroxisomes) and STING (at the endoplasmic reticulum). While the MAVS pathway has been mainly associated to the recognition of RNA viruses’ infections, the STING signalling is normally linked to the antiviral response against DNA viruses. Although controversial, there are evidences that a crosstalk between the STING pathway and the mitochondrial MAVS pathway exist. Our group has also recently demonstrated a direct interaction between STING and the peroxisomal MAVS. This thesis aimed to further study the possible crosstalk between the peroxisomal MAVS- and the STING-dependent antiviral pathways. Our research approach involved the specific activation of each of the two individual pathways and consequent analysis of the antiviral signalling originating from the other pathway: i) evaluation of the activation of the STING signalling pathway upon stimulation of the peroxisomal MAVS signalling; ii) evaluation the activation of the peroxisomal MAVS signalling pathway upon stimulation of the STING signalling. Our data suggests that no strong crosstalk occurs between the STING pathway and the MAVS pathway at peroxisomes. While more experiments are required to confirm this theory, this project has contributed to discover more details regarding the interplay between these two pathways at the peroxisome level, creating new opportunities for further experiments, which may enable the discovery of new targets for future therapeutics approaches.