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Restriction of HIV-1 infection in naturally resistant human cells

Objective

The life cycle of retroviruses is closely associated to a number of cellular processes of the host cell. Indeed, retroviruses have specifically evolved to exploit cellular mechanisms to avoid the defence systems of the cell. Conversely, eukaryotic cells have evolved several mechanisms to block the replication of HIV-1 or other related viruses. In contrast to CD4+ T-lymphocytes or macrophages, which are the preferential targets for HIV-1 infection, human placental trophoblast cells are not permissive to cell -free HIV-1 infection. Trophoblast cells hence constitute an important barrier for limiting mother-to-child HIV transmission.

The objectives of this proposal are to identify and characterise the mechanisms involved in the restriction of HIV-1 replication in these naturally resistant human cells. The restriction of cell-free HIV-1 infection in human trophoblast cells could be due to a defect in signalling occurring during actin microfilament polymerisation (necessary for the interaction with the transcription complex), a defect of virion intracellular trafficking after entry into the host cell that might lead to a delivery of the virus to a degradation pathway (endosomal or proteasomal pathway) or a direct block at the level of the of the reverse transcription. To study the mechanisms of this specific restriction, the BeWo cell line, derived from trophoblastic cells, will be employed.

The stage of the retroviral cycle at which the restriction occurs will be determined by using real-time PCR to detect and quantify early and late retrotranscripts. The project will investigate the colocalisation of virions with endosomal or lysosomal vesicles. The project will also address the existence of a potential intracellular restriction factor. The project should lead to a better understanding of the processes governing HIV infection and may lead to the development of novel therapeutic strategies to prevent infection.

Call for proposal

FP6-2005-MOBILITY-5
See other projects for this call

Coordinator

INSTITUT PASTEUR
Address
28, Rue Du Dr Roux
Paris
France