Changes in the accessibility of the HIV-1 Integrase C-terminus in the presence of cellular proteins

<p>Abstract</p> <p>Background</p> <p>Following entry, uncoating, and reverse transcription, a number of cellular proteins become associated with the Human Immunodeficiency Virus type 1 (HIV-1) pre-integration complex (PIC). With the goal of obtaining reagents for the analysis of the HIV-1 PIC composition and localisation, we have constructed functional integrase (IN) and matrix (MA) proteins that can be biotinylated during virus production and captured using streptavidin-coated beads.</p> <p>Results</p> <p>Although the labelled C-terminus allows for the sensitive detection of virion-associated IN, it becomes inaccessible in the presence of cellular proteins. This masking is not dependent on the nature of the tag and does not occur with the tagged MA. It was not observed either with an IN mutant unable to interact with LEDGF/p75, or when LEDGF/p75 was depleted from cells.</p> <p>Conclusion</p> <p>Our observation suggests that a structural rearrangement or oligomerization of the IN protein occurs during the early steps of infection and that this process is related to the presence of LEDGF/p75.</p

Gene transfer with lipospermines and polyethylenimines

International audienceIt is an obvious and basic principle that to be efficient, gene therapy requires effective gene transfer followed by adequate gene expression. However, getting DNA, a pro-drug, into the cell and into the nucleus, remains a crucially limiting factor. Even recombinant viral methods still show poor performances in clinical situations and non-viral methods are considered classically to be of yet lower efficiency. Here, we consider the mode of action, the nature of the complexes formed with DNA and the transfection potentials of two categories of inert, cationic vectors, the lipospermines and polyethylenimine. Both are among the best vectors currently available for in vitro work. Moreover, polyethylenimine is proving to be a versatile and effective carrier for different in vivo situations, especially for delivering genes into the mammalian brain

Taking lipospermines and polyethylenimine from in vitro to in vivo

International audienc