Stratégies d'échappement au système immunitaire du VIH.

Abstract

Les virus sont des ennemis des systemes immunitaires dans une guerre tres ancienne faite d' adaptations constantes aux armes et aux strategies de l' adversaire. Pour echapper a la detection et a la destruction par leur hote, les virus ont mis en place des mecanismes varies. Leur comprehension accroit nos connaissances sur les fonctionnements des systemes immunitaires et des virus. Les strategies mises en oeuvre par le virus de l' immunodeficience humaine (VIH) concernent notamment un processus-cle de la reponse immunitaire qui est la presentation antigenique par les molecules du complexe majeur d' histocompatibilite (CMH) aux lymphocytes T. Les cellules dendritiques sont des cellules specialisees dans la presentation antigenique possedant la propriete de mettre en route des reponses immunitaires. Dans l' infection par le VIH, les cellules dendritiques sont essentielles au virus pour sa penetration dans l' organisme, pour sa production et sa dissemination et, probablement, dans la pathogenie du SIDA.

HIV infection relies amazingly on dendritic cells (DC) for both, its replication and its ability to escape the immune system. DC are specialized in antigen presentation and possess the unique ability to stimulate naive T cells. In periphery, DC are spread in the skin and mucosae where they represent the first cells that HIV can infect. They efficiently contribute in its spreading by migrating to lymph nodes, a major site of infection. Infected DC can fuse with activated T cells to form syncitia that become fantastic factories of viral production. During the asymptomatic phase, follicular DC of lymph nodes trap HIV particles at their cell surface, representing the major reservoir of HIV. Thus, CD4+ T cells become infected by circulating through the dendritic network. HIV infection may impede DC capacity to present viral antigens and induces a decrease in DC numbers. Importantly, disappearance of DC is linked to the establishment of AIDS. Therefore, DC are key players at the different steps of the HIV infection. HIV particles incorporate several human proteins, including MHC class II molecules, when budding from infected cells. The role of these molecules is discussed in the light of recent results suggesting that they could be involved in the efficiency of virus entry as well as in neutralizing important components of the antiviral cellular response. Antigen presentation by MHC class II molecules might also be affected by the HIV infection. HIV has developed a strategy to down regulate surface MHC class I molecules, which allows infected cells to escape the cytotoxic response. This down modulation is mediated by the Nef protein, the expression of which modifies the intracellular trafficking of MHC class I molecules. Recent results suggest that Nef may connect them to the cellular machinery involved in transport to endocytic compartments from the plasma membrane as well as from the Golgi apparatus. Through its very high genomic variability, HIV creates numerous substitutions amongst the sequences encoding epitopes presented by MHC class I molecules and recognized by cytotoxic T cells. This may result in loss of presentation by MHC class I molecules, or in loss of T cell reactivity.