The general framework of the project NUCARCHIV is to use the recent development of nano-biotechnology to manipulate and image sophisticated in vitro reconstituted protein-nucleic acids complexes. Our goal is to bring several important advances in our understanding of the inner nucleoprotein structure (the nucleocapsid) of the human immunodeficiency virus (HIV), the causative agent of AIDS. The nucleocapsid complex plays essential roles during HIV assembly and early infection, and its modifications severely impede viral replication. The highly conserved nucleocapsid protein p7NC, the main actor of this complex, is considered as a prime target for developing new compounds with antiviral properties. Studies of nucleocapsid self-assembly, architecture and behavior in the host's cytoplasm are essential prerequisites for a complete description of HIV infection, and for the development of new anti-AIDS chemotherapies or vaccine. We will study by dynamic molecular imaging using atomic force microscopy single nucleoprotein complexes assembled from their purified partners (protein and nucleic acids templates). We will probe how these complexes are topologically modulated by the presence of viral enzymatic activities. Our goal is to provide a movie in real time showing the molecular dynamics of these complexes from virus maturation up to the late steps of early infection. We also propose to study the effect of a new molecule specifically designed to irreversibly inhibit HIV nucleocasid, with a potent application in AIDS prevention as component of next-generation of microbicids.
Field of science
- /natural sciences/biological sciences/microbiology/virology
- /medical and health sciences/health sciences/infectious disease/RNA virus/hiv
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
- /natural sciences/biological sciences/biochemistry/biomolecules/nucleic acid
Call for proposal
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