Molecular Mechanisms of HIV Pathogenesis
joint with HIV Vaccine Development: Progress and Prospects
Organizer(s): Beatrice H. Hahn, Wesley I. Sundquist, Michael H. Malim and Didier TronoDate: April 12 - 18, 2004
Location: Whistler Conference Centre, Whistler, BC, Canada
To replicate and cause disease, HIV-1 must overcome cellular and humoral immune responses, defeat innate cellular defense systems, usurp cellular factors, and reprogram the normal biology of the cell. Historically, detailed genetic analyses of viral functions and evolution have identified key viral determinants for the successful completion of each stage in the replication cycle. More recently, studies of innate antiviral and immune responses, host genetics, cell biology, and neuropathogenesis have identified host factors that HIV-1 must overcome in order to replicate. The field is now poised to combine these studies to define the molecular mechanisms that underlie important host/virus interactions, and our meeting therefore focuses on emerging concepts in the molecular mechanisms of HIV pathogenesis. Significant recent advances in this area include: the definition of a variety of envelope/receptor interactions, the development of tools for depleting cellular proteins and visualizing viral trafficking in real time, the discovery of cellular factors and genetic elements that restrict viral replication, an increased understanding of the activities of pathogenesis factors such as nef, the identification of host factors required for viral replication, assembly and budding, the development of non-pathogenic primate lentiviral models, and an increased understanding of the origins and evolution of HIV and primate lentiviruses in general. This recent progress opens the way to answering new questions: - How does the virus penetrate its target cells, once the envelope binds its receptors and undergoes an increasingly well characterized number of structural modifications? - What is the site and mechanism of uncoating, the step through which the inner components of viral cores lose their external layer, the capsid, and organize into an enzymatically active nucleoprotein complex? - How does the virus escape what increasingly appears to be a formidable attempt of the cell to repel this genetic invader? - How does the viral genome find its way to regions of the chromosome in which it is almost always successfully expressed? - How does the combination of host and viral factors modulate viral transcription and cell division, seemingly adapting it to the extracellular environment, and in some rare but critical cells resulting in latent, reactivatable gene expression? - How does the virus hijack intracellular machineries to organize the formation of new particles and promote their release from the infected cell? - What cells host the long-term reservoir of HIV that seems to preclude viral eradication in patients treated with highly active chemotherapy? - How do these cells avoid elimination by the immune system? - Why are naturally occurring SIV infections not causing disease in their natural hosts? - How can we best utilize these SIVs as tools to probe the pathogenic mechanisms of HIV? By bringing together a group of international leaders in HIV/AIDS research, new and exciting information in all of these areas will be presented, new paradigms will be established, and, perhaps, new approaches for anti-HIV therapeutics will be identified.
We gratefully acknowledge additional support for this conference from:
Bentham Science Publishers Ltd.