The interplay between human cytomegalovirus and peroxisomes: metabolism and membrane association with the endoplasmic reticulum

• Autor(a) principal: Silva, Beatriz Soares Carneiro da
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/25315
• topic: Peroxisomes; Cellular antiviral response; Cellular innate immunity; RIG-I; vMIA; Human cytomegalovirus; Inter-organelle communication; ACBD5; Endoplasmic reticulum

Peroxisomes are organelles responsible for key cellular metabolic functions, such as β-oxidation of very long-chain fatty acids, phospholipid synthesis and cellular redox balance. Peroxisomes have also been described as signalling platforms on the RIG-I-like receptors antiviral pathway. Upon infection, viral RNA is released into the cytoplasm where it is recognized by RIG-I-like receptors, which at the surface of mitochondria and peroxisomes induce the activation of MAVS. MAVS activation leads to a signalling cascade that culminates with the production of interferons and interferons-stimulated genes. Peroxisomes establish interactions with several organelles to maintain cellular homeostasis. Peroxisomes rely on the endoplasmic reticulum for their biogenesis, and recently it was described that ACBD5, a peroxisomal protein known to mediate the import of lipids into peroxisomes, interacts with VAPB, an endoplasmic reticulum protein. In this work, we study the effect of cellular antiviral defence activation over the peroxisomes metabolic functions. Moreover, we unravel the influence of the interaction between peroxisomes and endoplasmic reticulum. Our results suggest that peroxisomal metabolic functions are not affected by the activation of the peroxisome-dependent antiviral signalling. Yet, we observe that ACBD5 absence, which impairs interaction between peroxisomes and endoplasmic reticulum and is related with the transference of lipids between both organelles, dampens the antiviral response. Future studies to confirm the role of peroxisomes metabolic function upon infection, as well as the effect of ACBD5 on the cellular antiviral response, particularly to the peroxisomes-mediated signalling, are proposed.