Estudo do efeito modulador da noradrenalina e sinalização via receptor adrenérgico "2 sob a replicação do hiv-1 em linfócitos tcd4+ primários não ativados

• Ano de defesa: 2018
• Autor(a) principal: Almeida, Wanderley Alves de [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/48912/001300001pkq0
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Biologia molecular; Biologia celular; HIV
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6378356; https://repositorio.unifesp.br/handle/11600/53150

The human immunodeficiency virus (HIV1) has been a constant target of research for being the causative agent of a yet incurable disease – the acquired immunodeficiency syndrome (AIDS). Currently, latency is one of main obstacles for the virus eradication into HIV1 infected patients. Despite the efficiency on the antiviral treatment using the HAART, the HIV1 is capable to stablish the latent infection in the reservoir, escaping from the hosts immune response and antiretroviral therapy. Being so, the identification of the factors involved into these processes can provide new strategies for aids treatment, which interference on the infection’s early stages in order to inhibit or minimize the entrance and/or viral integration. Nowadays it is well stablished on literature that occurs intense immune and neuroendocrines systems integration and communication and that this interaction has a big biological importance in the course of autoimmune diseases, cancer and also microbial infections. One of the main interaction mechanisms between these two systems occurs through catecholamines release, noradrenaline in special, by nervous system and the main adrenergic receptor expressed by immune system’s cells seems to be the β2, although it has also been already reported the αadrenergic receptors’ expression in the innate immune system’s cells. In viral infections the whole of the adrenergics stimulation, besides little studied, is not yet well clarified. More specific to the HIV1, the adrenergic signalization’s effects had been contradictories: there are papers showing that these stimuli can both block and potentialize viral replication. The interaction study between HIV1 and the signalization through β2AR can give clues over the mechanisms which control viral latency and reactivation, yet today, not totally clarified. The present project had the main objective of investigating the noradrenaline’s modulating effect and signalization through β2adrenergic receptor under HIV1’ s replication in TCD4 lymphocytes and their possible participation on viral latency’s induction and reactivation’s processes. Our results show that the stimulation through β2AR before or after the viral infection is capable to induct HIV1’ s replication. We verified that this viral production is due to the signalization through β2AR and partially dependent from these receptor’s (through PKA) classic’s activation path