Since the Internet became available for commercial use in the early 90s, the way of doing business was changed forever. The Internet and electronic commerce have allowed people to carry out business by means of electronic communications, which makes it possible for them to do business and to conclude contracts with people situated within foreign jurisdictions. The need for consumer protection in electronic commerce has become necessary because of the misuse of aspects peculiar to electronic–commerce. Consumers have been cautious to make use of electroniccommerce, as they are uncertain about the consequences that their actions might have. Consumers will only utilise e–commerce if they have confidence in the legal system regulating it; therefore, legislation was needed to regulate their e–commerce activities. In 2002, the Electronic Communications and Transactions Act, 2002 was introduced into South African law as the first piece of legislation that would deal exclusively with electronic communications. Chapter VII of this particular act deals exclusively with consumer protection and seeks to remove certain uncertainties imposed by e–commerce. This is done by providing the South African consumer with statutory rights and obligations when engaging in electronic communications. The Consumer Protection Act, 68 of 2008 is the most recent piece of legislation that aims to promote a consistent legislative and enforcement framework relating to consumer transactions and agreements. South African legislation dealing with electronic commerce is relatively recent, and it is uncertain whether consumers are offered sufficient protection when they conclude contracts with suppliers or sellers from a foreign jurisdiction, that is, one that is situated outside South Africa. After looking at the protection mechanisms in place for South African consumers engaging in e–commerce, we have seen that there are certain problems that one might experience when trying to determine the applicability of some of the consumer protection measures to international electronic contracts. Most of the problems that we have identified are practical of nature. Consumers may, for instance, find it hard to execute their rights against foreign suppliers in a South African court, even if the court has jurisdiction to adjudicate the matter. Another problem that we identified is that some of the important terms in our legislation are too vaguely defined. Vague terms and definitions can lead to legal uncertainty, as consumers might find it hard to understand the ambit of the acts, and to determine the applicability thereof on their transactions. In order to look for possible solutions for South Africa, the author referred to the legal position with regards to consumer protections in the United Kingdom, and saw the important role that European Union legislation plays when determining the legal position regarding consumer protection in the UK. The legislation in the UK dealing with consumer protection is far more specific than the South African legislation dealing with same. There is definitely consumer protection legislation in place in South Africa but the ongoing technological changes in the electronic commerce milieu make it necessary for our legislators to review consumer protection legislation on a regular basis to ensure that it offers sufficient protection for South African consumers engaging in international electronic contracts. / Thesis (LL.M. (Import and Export Law))--North-West University, Potchefstroom Campus, 2012.

Since the Internet became available for commercial use in the early 90s, the way of doing business was changed forever. The Internet and electronic commerce have allowed people to carry out business by means of electronic communications, which makes it possible for them to do business and to conclude contracts with people situated within foreign jurisdictions. The need for consumer protection in electronic commerce has become necessary because of the misuse of aspects peculiar to electronic–commerce. Consumers have been cautious to make use of electroniccommerce, as they are uncertain about the consequences that their actions might have. Consumers will only utilise e–commerce if they have confidence in the legal system regulating it; therefore, legislation was needed to regulate their e–commerce activities. In 2002, the Electronic Communications and Transactions Act, 2002 was introduced into South African law as the first piece of legislation that would deal exclusively with electronic communications. Chapter VII of this particular act deals exclusively with consumer protection and seeks to remove certain uncertainties imposed by e–commerce. This is done by providing the South African consumer with statutory rights and obligations when engaging in electronic communications. The Consumer Protection Act, 68 of 2008 is the most recent piece of legislation that aims to promote a consistent legislative and enforcement framework relating to consumer transactions and agreements. South African legislation dealing with electronic commerce is relatively recent, and it is uncertain whether consumers are offered sufficient protection when they conclude contracts with suppliers or sellers from a foreign jurisdiction, that is, one that is situated outside South Africa. After looking at the protection mechanisms in place for South African consumers engaging in e–commerce, we have seen that there are certain problems that one might experience when trying to determine the applicability of some of the consumer protection measures to international electronic contracts. Most of the problems that we have identified are practical of nature. Consumers may, for instance, find it hard to execute their rights against foreign suppliers in a South African court, even if the court has jurisdiction to adjudicate the matter. Another problem that we identified is that some of the important terms in our legislation are too vaguely defined. Vague terms and definitions can lead to legal uncertainty, as consumers might find it hard to understand the ambit of the acts, and to determine the applicability thereof on their transactions. In order to look for possible solutions for South Africa, the author referred to the legal position with regards to consumer protections in the United Kingdom, and saw the important role that European Union legislation plays when determining the legal position regarding consumer protection in the UK. The legislation in the UK dealing with consumer protection is far more specific than the South African legislation dealing with same. There is definitely consumer protection legislation in place in South Africa but the ongoing technological changes in the electronic commerce milieu make it necessary for our legislators to review consumer protection legislation on a regular basis to ensure that it offers sufficient protection for South African consumers engaging in international electronic contracts. / Thesis (LL.M. (Import and Export Law))--North-West University, Potchefstroom Campus, 2012.

On the assumption that different registers of translated drama have different functions and that they therefore present information differently, the aim of the present study is to identify textual features that distinguish an Afrikaans stage translation from a page translation of Shakespeare's The Merchant of Venice. The first issue addressed concerns the nature and extent of lexical cohesion in these two registers. The second issue concerns my contention that the dialogue of a stage translation is more "involved". (Biber 1988) than that of a page translation. The research was conducted within the overall Descriptive Translation Studies (DTS) paradigm but the analytical frameworks by means of which these aims were accomplished were derived from text linguistics and register variation studies, making this an interdisciplinary study. Aspects of Hoey's ( 1991) bonding model, in particular, the classification of repetition links, were adapted so as to quantify lexical cohesion in the translations. Similarly, aspects of Biber's (1988) multi-dimensional approach to register variation were used to quantify linguistic features that signal involvement. The main finding of the study is that drama translation register (page or stage translation) does have a constraining effect on lexical cohesion and involved production. For Act IV of the play an overall higher density of lexical cohesion strategies was generated by the stage translation. In the case of the involved production features analysed, the overall finding was that the stage translation displayed more involvement than the page translation, to a statistically highly significant extent. The features analysed here cluster together sufficiently to reveal that in comparison with an Afrikaans page translation of a Shakespeare play, a recent stage translation displays a definite tendency towards a more oral, more involved and more situated style, reflecting no doubt a general modern trend towards creating more appropriate and accessible texts / Linguistics and Modern Languages / D. Litt. et Phil. (Translation Studies)

公私協力與自主規制在現代國家中，作為國家整體管制架構與管制行政之一環，有輔助國家行政機關之功能，減輕國家財力與人力之負擔，其有委託私人行使公權力者，則應有法律保留原則之適用，具公共目的存在與實現之關聯性與合比例性，方符合憲性之要件。若以組織法之規定，或無法律授權基礎之職權命令，均有違法治國之法律保留原則。在勞動契約上，政府透過法規範，對私法自治關係之勞動契約，以核備、備查或核定等之事前審查；在勞工保護上，課雇主以應作為與不作為之強制義務，及勞動三權之自主運作規範，協力與政府部門共同達成行政任務目標。 綜合本文研究，公私協力與自主規制在勞動法之實踐，係以公法規制私法，及容認私經濟主體在勞動關係之自主規制，連結公私部門關係，協力達成國家行政任務目標。這種公法介入私法關係，使私法形成之行政處分，作為保護勞工權益之行政處分，在勞動法上以勞基法第八十四條之一，有關勞雇約定書送地方主管機關核備之准駁行政處分。此行政處分導致勞雇間之私法關係變化，或與主管機關間之爭訟，其爭訟救濟之審判管轄權互有不同。 本研究有關建議摘要如下： 一、對勞動關係具成效之私經濟主體，毋寧採取自主規制方式，減少國家管制成本、降低資源耗費。 二、因法條文義不明致生重大爭議，主管機關之處理仍應具法律正當性。 三、公私協力與自主規制在勞動法之實踐，大抵以公法規制私法為基礎規範，主管機關執行上，仍須依循法律授權及法律明確性原則。 四、地方主管機關之行政裁量，不宜各自為政導致差異過大；且私法形成之行政處分，更應符合行政原則。

Environmental protection within specific proceedings pursuant the Building Act Unrestrained construction activity damages natural resources and diverse environmental components in irreversible or in difficult-to-repair ways, thereby further thwarting thriving or even surviving of the World population. In the Czech legal system, the regulatory measures of administrative bodies, along with the participation of the affected stakeholders, contribute to the environmental protection of the individual development project. This dissertation examines the methods, means, and tools of environmental protection within the framework of designated proceedings regulating the construction. Specifically, it analyzes the possibilities of implementing protective environmental measures within the construction-permitting procedures enshrined in the provisions of Sections 103 to 117 of the Building Act. Five construction-permitting regimes are examined separately: the building permit process; notification; public law contract; notification with certificate of the authorized inspector and projects requiring neither building permit nor notification. If followed lawfully, each of the regimes allows the prospect applicant to commence a relevant construction project. Permitting procedures are significantly influenced by...

Este trabalho analisa as políticas de EJA desenvolvidas pela União e pelo Estado de São Paulo, no período 2003-2009, sob a ótica do regime de colaboração em um Estado federativo. Elegemos como instâncias a serem objeto de nossa análise a Diretoria de Políticas de Educação de Jovens e Adultos da Secretaria de Educação Continuada, Diversidade e Alfabetização do Ministério da Educação DPEJA/SECAD/MEC, e a Secretaria de Estado da Educação de São Paulo SEESP. Através da descrição e análise de políticas e programas, e dos dados de demanda e oferta escolar por essas duas instâncias, buscamos avaliar como o regime de colaboração, entre as esferas federal e estadual de governo, tem se concretizado no Estado de São Paulo, no sentido e garantir a efetivação do direito à educação das pessoas jovens e adultas que não puderam iniciar ou concluir a escolarização básica na idade considerada regular. A pesquisa foi realizada mediante análise de documentos, realização de entrevistas com pessoas envolvidas com a temática e revisão da bibliografia sobre o tema. Conclui-se que a as responsabilidades estabelecidas pela legislação referente à obrigatoriedade da oferta de EJA não tem sido respeitada pela União e pelo Estado de São Paulo. Um dos principais fatores ligados a este descumprimento da legislação é o fato de que a colaboração entre estes dois entes federados em relação à EJA não se efetivou satisfatoriamente no período analisado. / educational policy; youth and adult education; federalism; São Paulo (State)

Este trabalho analisa as políticas de EJA desenvolvidas pela União e pelo Estado de São Paulo, no período 2003-2009, sob a ótica do regime de colaboração em um Estado federativo. Elegemos como instâncias a serem objeto de nossa análise a Diretoria de Políticas de Educação de Jovens e Adultos da Secretaria de Educação Continuada, Diversidade e Alfabetização do Ministério da Educação DPEJA/SECAD/MEC, e a Secretaria de Estado da Educação de São Paulo SEESP. Através da descrição e análise de políticas e programas, e dos dados de demanda e oferta escolar por essas duas instâncias, buscamos avaliar como o regime de colaboração, entre as esferas federal e estadual de governo, tem se concretizado no Estado de São Paulo, no sentido e garantir a efetivação do direito à educação das pessoas jovens e adultas que não puderam iniciar ou concluir a escolarização básica na idade considerada regular. A pesquisa foi realizada mediante análise de documentos, realização de entrevistas com pessoas envolvidas com a temática e revisão da bibliografia sobre o tema. Conclui-se que a as responsabilidades estabelecidas pela legislação referente à obrigatoriedade da oferta de EJA não tem sido respeitada pela União e pelo Estado de São Paulo. Um dos principais fatores ligados a este descumprimento da legislação é o fato de que a colaboração entre estes dois entes federados em relação à EJA não se efetivou satisfatoriamente no período analisado. / educational policy; youth and adult education; federalism; São Paulo (State)

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.