With the increasing demands of engaging in sustainability, the financial industry’s dominating market logic is currently being challenged. Banks are therefore experiencing demands to manage and legitimize sustainability, identified as containing both a market- and social logic, into a profit driven context. The aim of this study was thus to explore, at a micro level, how multiple logics of sustainability can be managed and legitimized in an organization where the dominant logic is being challenged. This was done by conducting a case study where the primary data was collected through semi-structured interviews with employees from Group Sustainable Finance (GSF) who are responsible for driving the sustainability agenda at Nordea. The results demonstrate that sustainability has been managed through a compromising strategy where elements of both the market- and social logic has been altered to appropriately suit the context characterized by profit maximization. During the process, an interesting finding evolved concerning how the micro perspective exposed the existence of conflicts within a single logic, defined as intra-logic conflicts. The results also contributed to identify stakeholder triggers as well as how normative-, instrumental-, and value rhetorical strategies are applied to legitimize Nordea’s sustainability practices.

Assurance of corporate sustainability reports relies on the idea of a third-party assuror who is independent and objective. The assurance approaches typically used by accountancy companies have been developed over many years and are supported by internal as well as external standards. With the help of these standards, the assuror provides credibility to the public statements of the companies through a thorough checking of statements, data and supporting systems. However, the orthodox approach overlooks or neglects the many paradoxes and dilemmas that are the daily experience of most assurors, e.g. what it means to be independent and objective while at the same time trying to develop a relation with the client. There has also been criticism of assurance, as currently practiced, as being too rigid, too predictable and providing too few benefits to the companies assured. In this thesis, the author explores why and how his own assurance practice differs from the more orthodox approach. This has led to the description of an alternative approach to assurance, called the ‘artist’ approach that takes the ethical dilemmas and paradoxes into account. The approach has been developed and described on the basis of the author’s own experiences using a critically reflexive methodology. The methodology builds on personal narratives and iterative feedback from fellow researchers and supervisors. The development of the ‘artist’ approach is based on: 1) a critical investigation into the idea of ‘compromise’, which leads to an alternative way of thinking about the practice of assurance; 2) a critical investigation into notions of trust and distrust, and power relations, and the effect of these on assurance work; and 3) a concept of ‘stumbling together’, which is built on relationality and ‘essential references’, where the assuror and the assuree are mutually exploring the territory. In the ‘artist’ approach, the values of independence and objectivity are compromised. The assuror actively strives to build personal trust based (at least in part) on technical kinship. Through this trust the power dynamics of the ‘insider’ and the ‘outsider’ are contained; indeed, the notion of ‘insider/outsider’ is forgotten in the moment. Independence has turned into interdependence, and objectivity into mutual engagement, where both assuror and assuree together might discover new issues not known to either of them before. In the orthodox approach, the assuree is ‘called to account’, whilst in the artist approach, the assuree is invited to ‘give an account’. This process of collaborative exploration allows the potential for radical new discoveries, for both assuror and assuree. The ‘artist’ approach as described here has affinities with complex responsive processes of relating as explained by Stacey. In the ‘artist’ approach, the craftsman approach is always paradoxically present at the same time, and the approach makes use of the same tools and the same framework as the craftsman approach. A wider understanding and application of the ‘artist’ approach can potentially lead to significant changes in the way assurors act, and hopefully to assurance results that are more relevant and useful.

Cette thèse porte sur les attaques par observations. Ces attaques étudient les variations d'émanation d'un composant pour retrouver une clé secrète. Ces émanations peuvent être multiples, par exemple, la consommation de courant électrique, le rayonnement électromagnétique, etc. Généralement, ces attaques font appel à des méthodes statistiques pour examiner la relation entre les émanations du composant et des modèles de consommation imaginés par l'attaquant. Trois axes sont développés dans cette thèse. Dans un premier temps, nous avons implémenté différentes attaques par observations sur des cartes graphiques en utilisant l'API OpenCL. Ces implémentations sont plus performantes que les implémentations classiques, ce qui permet à un attaquant de pouvoir traiter plus de données. Dans un second temps, nous avons proposé l'utilisation du MIC dans le cadre des attaques par observations. L'avantage du MIC, par rapport à l'information mutuelle, est sa facilité de calcul, ne dépendant pas de choix de noyau ou de taille de fenêtre. Son utilisation dans une attaque par observations est donc aisée, même si, la complexité des calculs à effectuer est souvent très importante. Enfin, nous avons introduit une nouvelle attaque, basée sur la distribution jointe de l'entrée et de la sortie de fonction cryptographique. Si cette distribution varie en fonction de la valeur de la clé impliquée par la fonction, on est capable de retrouver la clé secrète utilisée par le composant. Cette nouvelle attaque a la particularité de ne nécessiter ni la connaissance du texte clair, ni la connaissance du texte chiffré, ce qui lui permet d'être efficace même en présence de certaines contre-mesures. / The main subject of this manuscript is the Side Channel Attacks. These attacks investigate the variation of device emanations to retrieve a secret key. These emanations can be the power consumption, the electromagnetic radiation, etc. Most of the time, those attacks use statistical methods to examine the relationship between the emanations and some leakage models supposed by the attacker. Three main axis are developed here. First, we have implemented many side channel attacks on GPGPU using the API OpenCL. These implementations are more effective than the classical ones, so an attacker can exploit more data. Then, in order to provide a new side channel attack, we have suggested the use of a new dependency measurement proposed by Reshef et al., the MIC. The MIC is more advantageous than the mutual information, because its computation does not depend of a kernel choice nor a windows size. So, its use in side channel analysis is simple, even if the time complexity is large. Finally, we have introduced a new attack based on the join distribution of the input and the output of a cryptographic sub-function. If the distribution depends on the key used in the function, we can retrieve the secret key. This attack can be efficient even in presence of some countermeasures because it does not required the knowledge of both plain text or cipher text.

In a short time touchscreens has become one of the most used methods for input to smartphones and other machines such as cash registers, card terminals and ATMs. While the technology change was quick it introduces the possibility of new security holes. Compromising emanations is a possible security hole in almost all electronic equipment. These emanations can be used in a side-channel attack if they leak information that compromise the security of the device. This thesis studies a single-board computer (SBC) with a touchscreen and a smartphone in order to evaluate if any usable information leaks regarding what is done on the touchscreen i.e. where on the screen a user touches. It is shown that the location of a touch can be read out from information leaking through the power cable and wirelessly from the single-board computer. It is also shown that basic information can be read out wirelessly from the smartphone but further testing is required to evaluate the possibility to extract usable information from the device.

Many of us have grown up hearing or using words meant as insults or negative adjectives that were in fact names for social groups. Most of them have gone unquestioned in the mainstream consciousness, but the term Gay in the generally negative meaning has in the past years been given attention as offensive and homophobic, with debates emerging in response over whether or not this is true, particularly on the internet. It is the articles and forum threads from these debates that make out the empirical material for a qualitative study as I ask what these people’s thoughts are about this term and how it is perceived. After a qualitative coding and analysis of these texts, and interpretation of the results based on Erving Goffman’s theory of Phantom acceptance and stigma terms, Judith Butler’s theory of performativity, Ferdinand de Sassure’s theory of signifier and signified and how it connects to the community and Baudrillards theory of simulacra, this is the principal conclusion that I have drawn: For some of the people in this debate, the term Gay and its use is about homophobia and heterosexism, though mostly it’s not overt but a subconscious part of the continued dehumanization and stigmatization of homo- and bisexual people. This is a position I call The socially focused skepticism. Others distance themselves from this idea, talking about language development, the lack of inherent meaning of words and freedom of expression. Using Baudrillard for guidance, I interpret this as having a different, more abstract view of language than those who connect the term to heterosexism, and with this focus on language I name this position The language centered defense. Yet another group frame their reasoning about the term in compromise, preferring to limit their use of it to certain contexts rather than disposing the habit entirely or risk causing offense. To these people, whether or not the word is homophobic is less relevant to the discussion than showing respect for how it can be perceived, which gives their position the name The compromising position.

Genom ett undersökande experiment med elektromagnetisk sidokanalattack mot en knappsats för ett kommersiellt passersystem påvisas att informationsläckage i sidokanaler är ett fortsatt aktuellt problem och hur det gör fysisk åtkomstkontroll sårbart genom avlyssning och kopiering av användaruppgifter. Med enkel radioutrustning kan knapptryckningar registreras och avkodas genom oönskad elektromagnetisk strålning och teoretiskt är det möjligt att genomföra avlyssningen på en längre distans med särskilt utformad antenn och anpassad mottagare. Rapporten diskuterar problematiken med emission security hos konsumentprodukter som i militära sammanhang benämns Tempest eller RÖS (röjande signaler) och kräver kostsamma tester för att detekteras och hanteras. I regelverk för EMC (elektromagnetisk kompatibilitet) behandlas elektriska apparaters och näts utstrålning och påverkan av elektromagnetiska vågor, men inte direkt hur information kan läcka från informationsteknologisk utrustning vilket denna rapport vill problematisera. / Through an exploratory experiment using electromagnetic side-channel attack against a keypad for a commercial entry system it is demonstrated that information leakage through side-channels are an ongoing issue and may make entry systems vulnerable by recording of user data. Using simple radio equipment, keypresses can be recorded and decoded by undesired electromagnetic radiation and theoretically it is possible to carry out the attack on a longer distance with a specially designed antenna and a custom recieiver. The report discusses emission security in consumer products which in military context is termed Tempest or compromising emanations (Swedish: RÖS) and requires expensive tests to be detected and handled. The EMC regulations (electromagnetic compatibility) handles radiation and influence of electromagnetic waves in electronic apparatus and nets, but not directly how information can leak from information technology equipment which this report wants to problematize.

The purpose of the study was to construct a psycho-social model for team cohesion at a financial institution. The financial institution had been in existence for 127 years, and had faced significant challenges throughout its history of acquisitions and mergers to establish working teams that would give it a competitive edge in global financial markets. The research objective was to develop a psycho-social model for team cohesion by investigating the interrelationships and overall relationships amongst the independent constructs (self-worth, personality preferences and conflict resolution styles) and the relevant outcome (team cohesion). Furthermore, the study also scientifically tested the possible moderating effect of the employees’ socio-demographic characteristics (race, gender, age, level of education, job level and tenure) on the fostering of team cohesiveness. A quantitative cross-sectional survey design approach was selected and applied to a simple probability sample (N = 463) using standardised, valid and reliable measuring instruments. The population consisted of permanent employees, and the results revealed significant relationships between the construct variables. The canonical correlation indicated a significant overall relationship between the contingencies of self-worth domains, personality preferences and conflict resolution styles, and the team cohesion-related dispositions of cohesiveness and engaged. The structured equation modelling indicated a good fit of the data between the individuals’ contingencies of self-worth domains (family support, God’s love, virtues, competition, work competence, physical appearance and pleasing others), the accommodating conflict resolution style, an extraversion personality preference, and team cohesion. Hierarchical moderated regression showed that race, age, educational level and job tenure significantly moderated the relationship between the participants’ psycho-social attributes and team cohesion. Tests for significant mean differences revealed significant differences in terms of the socio-biographical variables. On a theoretical level, the study deepened understanding of the antecedent constructs (self-worth, personality preferences and conflict resolution styles) and team cohesion construct. On an empirical level, the study produced an empirically tested psycho-social model for team cohesion. This study will add significant practical, valuable knowledge to the organisation in managing the future establishment and enhancement of team cohesion, and when integrating new team members to the environment during organisational restructuring and re-alignment after acquisitions and mergers, without negatively affecting organisational effectiveness. These findings invariably provided new insight in managing and understanding inherent interpersonal conflict among employees in the workplace and the enhancement of team cohesion practices, thus adding to the existing body of knowledge in the fields of Consulting Psychology and Industrial and Organisational Psychology, more specifically in financial organisations. / Psychology / D. Phil. (Consulting Psychology)

<p dir="ltr">Unintentional electromagnetic emission (called emanation) from electronic devices and cables contains a significant correlation with the source signal and can be used to recover otherwise confidential data. In our work, EM emanation has been exploited to recover keystrokes from USB keyboards. Also, such emission has been utilized to form a covert channel for data exfiltration from air-gapped devices without being detected by IDS. To protect sensitive information, an automated emanation detection system has been proposed by developing two emanation detection algorithms (CNN-based and harmonic-based) through the characterization of emanation signals from a wide range of devices. Apart from emanation, data theft can happen due to the failure of access control methods. Traditional wireless devices are susceptible to various spoofing attacks as they only use digital signature-based authentication systems, ignoring the physical signatures completely. To circumvent that, RF-PUF was proposed to use device-specific signatures to be used for trust augmentation in traditional methods. By forming an extensive experimental dataset, we established RF-PUF as a strong PUF with a low-power overhead that outperformed the state-of-the-art methods and is robust against typical attacks. For real-time authentication, we proposed DIRAC, which forms dynamic device clusters and incrementally learns as more device data becomes available. Since our root of trust is in the physical signature of the ICs, they also need to be secured. However, counterfeited ICs may jeopardize that goal. We have proposed RF-PSF, which uses device-specific physical properties to authenticate its process technology which is a big part of the cloned IC detection.</p>

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.