Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses
Autor(a) principal: | |
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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 |
Resumo: | 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. |
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Deciphering the crosstalk between MAVS- and STING- dependent antiviral responsesVirusesReroxisomesAntiviral immunityMAVSSTINGPeroxisomes 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.Os peroxissomas são organelos intracelulares dinâmicos, essenciais para várias funções celulares, e que estão associados a diferentes processos patológicos. Este organelo também foi descrito como sendo uma importante plataforma de sinalização para a resposta antiviral celular. Após a entrada do vírus, os recetores citosólicos, como o RIG-I ou o cGAS, detetam os ácidos nucleicos virais, ativando respetivamente as vias de sinalização dependentes das proteínas adaptadoras MAVS (nos peroxissomas e na mitocôndria) e STING (no retículo endoplasmático). Enquanto a via da MAVS foi principalmente associada à restrição da infeção por vírus de RNA, a sinalização da STING é normalmente associada à resposta antiviral contra vírus de DNA. Contudo, evidências de uma ligação entre ambas as vias existem. O nosso grupo demonstrou recentemente que a MAVS peroxissomal interage diretamente com STING. Esta tese teve como objetivo continuar a estudar a possível interação entre as vias antivirais dependentes da MAVS peroxissomal e da STING. A nossa abordagem envolveu a ativação específica de uma das duas vias e consequentemente a análise da origem da sinalização antiviral originada na outra via: i) avaliação da ativação da via de sinalização da STING após a estimulação da via da MAVS peroxissomal; ii) avaliação da ativação da via de sinalização da MAVS peroxissomal após estimulação da via da STING. Os nossos resultados sugerem que não existe uma interação entre a via da STING e a via da MAVS nos peroxissomas. Apesar de mais experiências serem necessárias para confirmar esta hipótese, este projeto contribuiu para desvendar em mais detalhe as interações entre estas duas vias ao nível do peroxissoma, criando novas oportunidades para mais experiências que poderão levar à descoberta de novos alvos para futuras abordagens terapêuticas.2024-12-21T00:00:00Z2022-12-15T00:00:00Z2022-12-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/35967engFerreira, Rui Filipe Tavaresinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:09:30Zoai:ria.ua.pt:10773/35967Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:06:58.345621Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses |
title |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses |
spellingShingle |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses Ferreira, Rui Filipe Tavares Viruses Reroxisomes Antiviral immunity MAVS STING |
title_short |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses |
title_full |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses |
title_fullStr |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses |
title_full_unstemmed |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses |
title_sort |
Deciphering the crosstalk between MAVS- and STING- dependent antiviral responses |
author |
Ferreira, Rui Filipe Tavares |
author_facet |
Ferreira, Rui Filipe Tavares |
author_role |
author |
dc.contributor.author.fl_str_mv |
Ferreira, Rui Filipe Tavares |
dc.subject.por.fl_str_mv |
Viruses Reroxisomes Antiviral immunity MAVS STING |
topic |
Viruses Reroxisomes Antiviral immunity MAVS STING |
description |
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. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-15T00:00:00Z 2022-12-15 2024-12-21T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/35967 |
url |
http://hdl.handle.net/10773/35967 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799137724956934144 |