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Autophagy in the patogenesis of HIV infection
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O Vírus da Imunodeficiência Humana (HIV) é um dos patogenos humanos mais fatais do mundo, com 940 mil mortes por ano. Desde o início da epidemia, na década de 1980, mais de 70 milhões de pessoas foram infetadas pelo HIV e cerca de 35 milhões de pessoas morreram devido ao HIV. Ao longo dos anos, a autofagia, um processo lisossomal catabólico essencial para a manutenção da homeostase celular, tem emergido como um importante mecanismo de defesa do hospedeiro contra a infeção pelo HIV, não só através da degradação dos patógenos invasores (xenofagia), mas também pela indução da imunidade inata e adaptativa. No entanto, há evidências de que o vírus possui vários mecanismos contra a autofagia que podem evitar e perturbar o mecanismo de autofagia. O HIV-1 infecta linfócitos T CD4+, macrófagos e células dendríticas, causando a falha do sistema imunológico. O vírus pode também infetar células do Sistema Nervoso Central, o que provoca neurodegeneração. Vários estudos indicam que a neurodegeneração observada na infeção pelo HIV-1 está associada à desregulação da autofagia neuronal. Por todas estas razões, a modulação da autofagia está a ser alvo de investigação para o tratamento de doenças infeciosas. Devido à capacidade da autofagia de atuar ao nível da degradação intracelular de patógenos, a modulação da autofagia pode potencialmente melhorar o resultado dos tratamentos atuais antirretrovirais para tratar a infeção pelo HIV. Esta monografia através de pesquisa bibliográfica aborda os principais aspetos da autofagia na patogénese da infeção pelo HIV, agrupando a informação mais relevante sobre a temática, sendo o principal objetivo reunir evidência de que a autofagia é uma via celular que pode ser modulada para novas terapêuticas e vacinas contra o HIV-1.
Human Immunodeficiency Virus (HIV) is among the most lethal human pathogens worldwide with 940 thousand deaths per year. Since the beginning of the epidemic, in the 80's, more than 70 million people have been infected with HIV and about 35 million people have died of HIV. Over the years, autophagy, a lysosomal catabolic process essential for maintaining cellular homeostasis, has emerged as a major host defence mechanism against HIV infection not only through lysosomal degradation of invading pathogens (xenophagy) but also in the induction of innate and adaptive immunity pathways. However, there is evidence that the virus proteins deploy various countermeasures against autophagy, which can perturb and avoid autophagy mechanism. HIV-1 infects CD4+ T cells, macrophages and dendritic cells, causing the failure of the immune system. Furthermore, the virus can also infect nervous system cells, which leads to neurodegeneration. Several studies have also indicated that neurodegeneration seen in HIV-1 infection is associated with dysregulation of neuronal autophagy. Therefore, the modulation of autophagy is being investigated for the treatment of many infectious diseases. Given the capacity of autophagy to act at the host cellular level to improve intracellular killing pathogens, modulating autophagy may potentially improve the outcome of the current antiretroviral therapies to treat HIV infection. The purpose of this monography is to develop a bibliographic review focusing on the key points of the autophagy in the pathogenesis of HIV infection, grouping the most relevant information on this matter. The main objective is to gather evidence that autophagy is a cellular pathway that could potentially be modulated for HIV-1 therapy and vaccine.
Human Immunodeficiency Virus (HIV) is among the most lethal human pathogens worldwide with 940 thousand deaths per year. Since the beginning of the epidemic, in the 80's, more than 70 million people have been infected with HIV and about 35 million people have died of HIV. Over the years, autophagy, a lysosomal catabolic process essential for maintaining cellular homeostasis, has emerged as a major host defence mechanism against HIV infection not only through lysosomal degradation of invading pathogens (xenophagy) but also in the induction of innate and adaptive immunity pathways. However, there is evidence that the virus proteins deploy various countermeasures against autophagy, which can perturb and avoid autophagy mechanism. HIV-1 infects CD4+ T cells, macrophages and dendritic cells, causing the failure of the immune system. Furthermore, the virus can also infect nervous system cells, which leads to neurodegeneration. Several studies have also indicated that neurodegeneration seen in HIV-1 infection is associated with dysregulation of neuronal autophagy. Therefore, the modulation of autophagy is being investigated for the treatment of many infectious diseases. Given the capacity of autophagy to act at the host cellular level to improve intracellular killing pathogens, modulating autophagy may potentially improve the outcome of the current antiretroviral therapies to treat HIV infection. The purpose of this monography is to develop a bibliographic review focusing on the key points of the autophagy in the pathogenesis of HIV infection, grouping the most relevant information on this matter. The main objective is to gather evidence that autophagy is a cellular pathway that could potentially be modulated for HIV-1 therapy and vaccine.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
HIV Autophagy Neurodegeneration HIV-1 therapy Immune response. Mestrado Integrado - 2019