Il s'agira d'envisager, en français, l'oeuvre du philosophe allemand Eugen Fink (1905-1975), dont le corpus complet n'est disponible qu'en allemand. Ce sera donc une "introduction" à sa pensée. A cet égard nous nous demanderons quelle est la continuité de la pensée dite du jeune Fink et de celle du Fink dit "de la maturité". Nous montrerons, contre certains préjugés, la continuité problématique, - cosmologique -, du penseur allemand. A la lumière de l'oeuvre ultérieure nous proposerons d'abord une nouvelle interprétation de la pensée du jeune Fink en même temps que son originalité vis à vis des maitres de Fribourg (Husserl, Heidegger). Dans une seconde partie nous exposerons une structure problématique que nous soutenons être celle du Fink de la maturité: d'abord une théorie du questionnement métaphysique, à la lumière de laquelle Fink réevalue les problèmes philosophiques fondamentaux: c'est à dire d'abord une cosmologie originale, une théorie de la phénoménalité fondamentale, à partir desquelles Fink repense de façon originale l'histoire de la métaphysique (antique et moderne). Après un appendice sur son interprétation de Nietzsche (qui prend son sens dans ce qui précède), nous concluerons sur sa position sur les problèmes qui lui furent contemporains (anthropologie et ontologie). / Tue purpose of this work is to introduce in french to german thinker Eugen Fink (1905-1975), which is most unknow in french. We will see the relation between the "young" Fink and the "old" Fink, and the continuity between the both period of his thought. First we will read newly the classics texts of the young Fink, and show the cosmological dimension of his thought, and then we will see how the "old" Fink drive his philosophy: with a theory, - new -, of the philosophical wondering, which drive to a new cosmology; from here, Fink read and think newly the history of metaphysics. To end, we will compare the Fink's thought with the theory of the man, from one side, and with the ontology of the last Heidegger, from the other side. This will be the first introduction to the whole Fink's thought in french.

"The question of locus standi regarding the non-state complaints procedure before the African Commission on Human and Peoples' Rights (the Commission) is a very flexibile one. Although the language of the African Charter on Human and Peoples' Rights (the Charter), the enabling powers and functions of the Commission, does not provide for such broad standing, the Commission has over its 20 years of operation, given broad interpretation to the question of standing by adopting the actio popularis doctrine. As a reslut the Commission has entertained communicatons from any person, group of persons or non-governmental organisation (NGOs), whether on their own behalf or on behalf of tothers. The location or nationality of such persons is also not a bar to standing. Consequently, the Commission has accepted communications from national NGOs operating in the country of the state party against whom the complaint is made, NGOs with a regaional focus, international NGOs, and non-African nationals. ... The study has five chapters. Chapter one introduces the study and the justification thereof. Chapter two explores the origin, nature and application of locus standi in domestic legal systems with particluar respect to private protection of public rights and human rights protection using Ghana, Mozambique and South Africa as case studies. Chapter three examines the standing requirements before other regional human rights protection systems namely the ECHR, and the IACHR as well as global human rights protection mechanisms throught the lens of the HRC, the CERD-Committee, the CAT-Committee and the CEDAW-Committee. Chapter four traces and assesses the development of the broad standing requirements before the Commission regarding its non-state communications procedure and the problems associated with them. And Chapter five presents the conclusions and recommendations of the study." -- Introduction. / Thesis (LLM (Human Rights and Democratisation in Africa)) -- University of Pretoria, 2006. / Prepared under the supervision of Mr. Angelo Matusse at the Faculty of Law, Universidade Eduardo Mondlane, Maputo, Mozambique / http://www.chr.up.ac.za/academic_pro/llm1/dissertations.html / Centre for Human Rights / LLM

M arrived in Sweden as a hopeful and aspiring adolescent minor in 2015. By 2022, he instead finds himself living on the streets as a drug addict, homeless, with his residency permit rejected and his asylum application declined. This thesis analyzes his situation through a theory of Performativity and Affect, foremost leaning on Judith Butler, Lauren Berlant, and Sara Ahmed. It scrutinizes the role of the imagined Refugee Figure that M came to represent. It is produced through a set of interviews while following Lee Ann Fujii’s method of Relational Interviewing. While the role for M is being outlawed to the exterior of Global Politics, without the ability to appear, he is consequently never valued as a matter of consideration. May other routes have been possible? The Refugee Figure is here contrasted to alternative figurative identities, such as the builder or even the desperado, that more naturally are associated with an ability to act and to be seen. Ultimately, the thesis reads precarious mobility as an expression of political will, agency, and a voice with one’s feet.

La première partie de l’étude est consacrée à l’invocation, intra et extra muros, du droit à un procès équitable. Sont analysés ainsi, dans un premier temps, l’applicabilité directe de l’article 6 et la subsidiarité de la Convention par rapport au droit national et de la Cour Européenne des Droits de l’Homme par rapport aux juridictions nationales. Le droit à un procès équitable étant un droit jurisprudentiel, l’étude se focalise, dans un second temps, sur l’invocabilité des arrêts de la Cour Européenne et plus précisément sur l’invocabilité directe de l’arrêt qui constate une violation du droit à un procès équitable dans une affaire mettant en cause l’Etat et l’invocabilité de l’interprétation conforme à l’arrêt qui interprète l’article 6 dans une affaire mettant en cause un Etat tiers. L’introduction dans l’ordre juridique français et hellénique de la possibilité de réexamen de la décision pénale définitive rendue en violation de la Convention a fait naitre un nouveau droit d’accès à la Cour de cassation lequel trouve son terrain de prédilection aux violations de l’article 6 et constitue peut-être le pas le plus important pour le respect du droit à un procès équitable après l’acceptation (par la France et la Grèce) du droit de recours individuel. Quant au faible fondement de l’autorité de la chose interprétée par la Cour Européenne, qui est d’ailleurs un concept d’origine communautaire, cela explique pourquoi un dialogue indirect entre la Cour Européenne et la Cour de cassation est possible sans pour autant changer en rien l’invocabilité de l’interprétation conforme et le fait que l’existence d’un précédent oblige la Cour de cassation à motiver l’interprétation divergente qu’elle a adoptée.La seconde partie de l’étude, qui est plus volumineuse, est consacrée aux garanties de bonne administration de la justice (article 6§1), à la présomption d’innocence (article 6§2), aux droits qui trouvent leur fondement conventionnel dans l’article 6§1 mais leur fondement logique dans la présomption d’innocence et aux droits de la défense (article 6§3). Sont ainsi analysés le droit à un tribunal indépendant, impartial et établi par la loi, le délai raisonnable, le principe de l’égalité des armes, le droit à une procédure contradictoire, le droit de la défense d’avoir la parole en dernier, la publicité de l’audience et du prononcé des jugements et arrêts, l’obligation de motivation des décisions, la présomption d’innocence, dans sa dimension procédurale et personnelle, le « droit au mensonge », le droit de l’accusé de se taire et de ne pas contribuer à son auto-incrimination, son droit d’être informé de la nature et de la cause de l’accusation et de la requalification envisagée des faits, son droit au temps et aux facilités nécessaires à la préparation de la défense, y compris notamment la confidentialité de ses communications avec son avocat et le droit d’accès au dossier, son droit de comparaître en personne au procès, le droit de la défense avec ou sans l’assistance d’un avocat, le droit de l’accusé d’être représenté en son absence par son avocat, le droit à l’assistance gratuite d’un avocat lorsque la situation économique de l’accusé ne permet pas le recours à l’assistance d’un avocat mais les intérêts de la justice l’exigent, le droit d’interroger ou faire interroger les témoins à charge et d’obtenir la convocation et l’interrogation des témoins à décharge dans les mêmes conditions que les témoins à charge et le droit à l’interprétation et à la traduction des pièces essentielles du dossier. L’analyse est basée sur la jurisprudence strasbourgeoise et centrée sur la position qu’adoptent la Cour de cassation française et l’Aréopage. / The first party of the study is dedicated to the invocation of the right to a fair trial intra and extra muros and, on this basis, it focuses on the direct applicability of Article 6 and the subsidiarity of the Convention and of the European Court of Human Rights. Because of the fact that the right to a fair trial is a ‘‘judge-made law’’, the study also focuses on the invocability of the judgments of the European Court and more precisely on the direct invocability of the European Court’s judgment finding that there has been a violation of the Convention and on the request for an interpretation in accordance with the European Court’s decisions. The possibility of reviewing the criminal judgment made in violation of the Convention has generated a new right of access to the Court of cassation which particularly concerns the violations of the right to a fair trial and is probably the most important step for the respect of the right to a fair trial after enabling the right of individual petition. As for the weak conventional basis of the authority of res interpretata (“autorité de la chose interprétée”), this fact explains why an indirect dialogue between the ECHR and the Court of cassation is possible but doesn’t affect the applicant’s right to request an interpretation in accordance with the Court’s decisions and the duty of the Court of cassation to explain why it has decided to depart from the (non-binding) precedent.The second party of the study is bigger than the first one and is dedicated to the guarantees of the proper administration of justice (Article 6§1), the presumption of innocence (Article 6§2), the rights which find their conventional basis on the Article 6§1 but their logical explanation to the presumption of innocence and the rights of defence (Article 6§3). More precisely, the second party of the study is analyzing the right to an independent and impartial tribunal established by law, the right to a hearing within a reasonable time, the principle of equality of arms, the right to adversarial proceedings, the right of the defence to the last word, the right to a public hearing and a public pronouncement of the judgement, the judge’s duty to state the reasons for his decision, the presumption of innocence, in both its procedural and personal dimensions, the accused’s right to lie, his right to remain silent, his right against self-incrimination, his right to be informed of the nature and the cause of the accusation and the potential re-characterisation of the facts, his right to have adequate time and facilities for the preparation of the defence, including in particular the access to the case-file and the free and confidential communication with his lawyer, his right to appear in person at the trial, his right to defend either in person or through legal assistance, his right to be represented by his counsel, his right to free legal aid if he hasn’t sufficient means to pay for legal assistance but the interests of justice so require, his right to examine or have examined witnesses against him and to obtain the attendance and examination of witnesses on his behalf under the same conditions as witnesses against him and his right to the free assistance of an interpreter and to the translation of the key documents. The analysis is based on the decisions of the European Court of Human Rights and focuses on the position taken by the French and the Greek Court of Cassation (Areopagus) on each one of the above mentioned rights.

O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal. / The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.

O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal. / The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.