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129 HIV and Immune System Deregulation

Rizos, Apostolos K1; Morikis, Dimitrios2; Krambovitis, Elias3

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 52
doi: 10.1097/01.qai.0000397317.47707.c2
Abstracts
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1University of Crete, Department of Chemistry, Heraklion, GREECE; 2University of California, Riverside, Riverside, CA, USA; 3University of Thessaly, School of Health Sciences, Karditsa, GREECE

Tremendous advances have been made over the last decade in our understanding of the complex interaction between the human immunodeficiency virus (HIV) and the host immune system that has laid ground for the development of new potent antiviral drugs. However, many central questions that bear on the feasibility of developing an HIV vaccine still remain unanswered, including identification of protective immune mechanisms, addressing the high variability of the virus and its ability to evade immune responses. In this context the most important unanswered question is the mechanism by which HIV inactivates or kills T cells. It is now well established that the third hypervariable domain (V3) of the human immunodeficiency virus-1 (HIV-1) glycoprotein gp120 plays a crucial role in the cell attachment mechanism of the virus. Using synthetic peptides we have shown that during the process of specific antigen presentation, the presence of the cationic crown of V3 induces enhanced and accelerated activation of the responding CD4+ T cells, followed by a sharp apoptosis. The degree of activation was related to the cationic potential of the V3 peptide. The interacting molecule on the T cell membrane was the chemokine receptor CCR5 which also acts as co receptor to the virus. This interaction is central to immune dysfunction caused by the presence of the virus and is a major contributor to the HIV-1 pathogenesis. A careful appraisal of the structure and dynamics between gp120 and CCR5 using physicochemical methods gave new insights of the underlying interactions at a molecular level and will contribute to our ability to intervene and develop novel therapeutic approaches against this infection.

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