Cellular responses to viral infection : proteostasis and innate immunity

• Autor(a) principal: Marques, Mariana Campos
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/22054
• topic: Doenças virais - Virus diseases; Doenças contagiosas

Viruses are small opportunistic infectious agents. Virus entry, replication and assembly are dynamic and coordinated processes that require precise interactions with host components, often with cellular organelles. Hence, we proposed to study two different viruses affecting two distinct cellular surveillance mechanisms: Human Cytomegalovirus (HCMV) and Influenza A Virus (IAV) influence on the innate immune response and proteostasis, respectively. HCMV might be associated with additional long-term health consequences in human due to its ability to establish a lifelong persistent latent infection. HCMV encodes vMIA, an anti-apoptotic protein known to co-localize at peroxisomes and mitochondria, induce their fragmentation and inhibit the downstream cellular antiviral response that is established at both organelles. In the present work, we aimed to characterize the role of vMIA in the peroxisomal-MAVS dependent antiviral response. We proposed to map the vMIA domains responsible for the organelles’ morphology changes and innate immune response inhibition. Our results revealed that the 115-130 amino acid sequence might be important for the organelles’ fragmentation. We also found that m38.5, an analogue of vMIA in murine CMV (MCMV) seems to localize at peroxisomes, induce the organelle’s fragmentation and clearly inhibit the peroxisome-dependent antiviral immune response. These results suggest that this virus may be useful to complement our results with experiments performed in animals or in the context of a viral infection. IAV is the causative agent for most of the annual epidemic in humans. During IAV infection, it occurs the accumulation of unfolded proteins and the formation of specialized sites of viral replication, resulting in the formation of insoluble aggregates or inclusions. In this study, we proposed to determine whether and how IAV infection leads to aggresomal-prone proteins accumulation. Our preliminary results suggest aggresomes formation during viral infection, previous to the vRNP release in to the cytoplasm.