HIV/AIDS | EPFL Graph Search

Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual may not notice any symptoms, or may experience a brief period of influenza-like illness. Typically, this is followed by a prolonged incubation period with no symptoms. If the infection progresses, it interferes more with the immune system, increasing the risk of developing common infections such as tuberculosis, as well as other opportunistic infections, and tumors which are rare in people who have normal immune function. These late symptoms of infection are referred to as acquired immunodeficiency syndrome (AIDS). This stage is often also associated with unintended weight loss. HIV is spread primarily by unprotected sex (including anal and vaginal sex), cont

Comprendre la société-Monde par ses enjeux et ses acteurs

Olivier Vilaça

The aim of this thesis is to understand the World as a full-fledged object, namely as the space of a society. This objective is at the same time necessary and problematic. It is necessary because the sudden end of the Cold War entailed the need of new conceptual frameworks to understand the World without the confrontation of two ideological blocs. In parallel, the acceleration of globalization based on transnational and reticular processes profoundly questioned the apportionment of the World in territories and the classical distinction between the national and international spheres. This phenomenon also brought about the emergence of social issues (such as AIDS and climate change) and of non-state actors (such as globalized companies and Non-Governmental Organizations) which cannot be understood without taking into account their global dimension. Faced with these profound changes, it is important to be able to apprehend the World in its global dimension, going beyond its economic aspects. The so-called Global society model, which considers the existence of a global society as a possible option, allows this. However, the methodological nationalism – on which social sciences were based and according to which each society is necessarily linked with a territory, a State and a nation – makes it difficult to use this model to understand the World. Social sciences concepts, theories and methods were developed to conceive the World as a sum of objects (i.e. states, civilizations) and not as a full-fledged object. To go beyond this limit, the approach of this thesis is to apprehend the World through its issues and actors. In particular, I tried to understand if, and how, the involvement of the Lafarge company in the fight against the HIV/AIDS epidemic between 2002 and 2005 contributed to the development of a global society. Through the results of participant observation and an analysis of non-directive interviews with managers from Lafarge who were involved in the development of the company's AIDS program, I identified three main contributions to the emergence of a global society. First, the company contributed to the social construction of the AIDS epidemic as a global issue : in particular, the global approach the company adopted to deal with the AIDS epidemic was notably different from its traditional modus operandi in the field of social responsibility based on a local and decentralized approach. In addition, through its decision to provide its employees, their families and sometimes local communities with antiretroviral treatments in certain circumstances, the company participated in global controversies on cost-effectiveness of triple therapy, use of generic drugs and health as a global public good. Second, Lafarge's AIDS program contributed to reinforce the global dimension of the group, mainly by providing the power of the corporate with legitimacy, but also by contributing to the development of a global identity and by promoting interactions among subsidiaries. Third, the company contributed to building a global political arena, in particular through its interactions with a series of other global actors belonging to the same responsibility community. These interactions created legitimacy, transparency, institutions and norms at the global level, contributing to the emergence of a transnational deliberative arena. This thesis thus shows that it is possible to view the world as a full-fledged object and to overcome methodological nationalism by studying transnational objects, such as a globalized company and a global issue. It shows that Lafarge's involvement in the fight against AIDS contributes to the emergence of a global societal reference with a strong political dimension.

EPFL2009

A Baseline Cellular Antiviral State Is Maintained by cGAS and Its Most Frequent Naturally Occurring Variant rs610913

Jacques Fellay, Christian Axel Wandall Thorball, Shuting Xu

Upon recognition of aberrantly located DNA, the innate immune sensor cyclic GMP-AMP synthase (cGAS) activates stimulator of IFN genes (STING)/IFN regulatory factor (IRF)3-driven antiviral responses. In this study, we characterized the ability of a specific variant of the human cGAS-encoding gene MB21D1, rs610913, to alter cGAS-mediated DNA sensing and viral infection. rs610913 is a frequent G>T polymorphism resulting in a P261H exchange in the cGAS protein. Data from the International Collaboration for the Genomics of HIV suggested that rs610913 nominally associates with HIV-1 acquisition in vivo. Molecular modeling of cGAS(P261H) hinted toward the possibility for an additional binding site for a potential cellular cofactor in cGAS dimers. However, cGAS(wild-type [WT]) or cGAS(P261H)-reconstituted THP-1 cGAS knockout cells shared steady-state expression of IFN-stimulated genes, as opposed to cells expressing the enzymatically inactive cGAS(G212A/S(213)A). Accordingly, cGAS(WT) and cGAS(P261H) cells were less susceptible to lentiviral transduction and infection with HIV-1, HSV-1, and Chikungunya virus as compared with cGAS knockout or cGAS(G212A/S(213)A) cells. Upon DNA challenge, innate immune activation appeared to be mildly reduced upon expression of cGAS(P261H) compared with cGAS(WT). Finally, DNA challenge of PBMCs from donors homozygously expressing rs610913 provoked a trend toward a slightly reduced type I IFN response as compared with PBMCs from GG donors. Taken together, the steady-state activity of cGAS maintains a baseline antiviral state rendering cells more refractory to IFN-stimulated gene-sensitive viral infections. rs610913 failed to grossly differ phenotypically from the WT gene, suggesting that cGAS(P261H) and WT cGAS share a similar ability to sense viral infections in vivo.

AMER ASSOC IMMUNOLOGISTS2022

Inhibition of HIV-1 multiplication by a modified U7 snRNA inducing Tat and Rev exon skipping

Didier Trono

The HIV-1 regulatory proteins Tat and Rev are encoded by multiply spliced mRNAs that differ by the use of alternative 3' splice sites at the beginning of the internal exon. If these internal exons are skipped, the expression of these genes, and hence HIV-1 multiplication, should be inhibited. We have previously developed a strategy, based on antisense derivatives of U7 small nuclear RNA, that allows us to induce the skipping of an internal exon in virtually any gene. Here, we have successfully applied this approach to induce a partial skipping of the Tat, Rev (and Nef) internal exons. Three functional U7 constructs were subcloned into a lentiviral vector. Two of them strongly reduced the efficiency of lentiviral particle production compared to vectors carrying either no U7 insert or unrelated U7 cassettes. This defect could be partly or fully compensated by coexpressing Rev from an unspliced mRNA in the producing cell line. Upon stable transduction into CEM-SS or CEM T-lymphocytes, the most efficient of these constructs inhibits HIV-1 multiplication. Although the inhibition is not complete, it is more efficient in combination with another mechanism inhibiting HIV multiplication. Therefore, this new approach targeting HIV-1 regulatory genes at the level of pre-mRNA splicing, in combination with other antiviral strategies, may be a useful new tool in the fight against HIV/AIDS.

Wiley-Blackwell2007