John Libbey Eurotext

Virologie

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L’impact du niveau d’expression du corécepteur CCR5 sur l’histoire naturelle de l’infection par VIH Volume 10, issue 4, Juillet-Août 2006

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Laboratoire d’immunologie, Hôpital Saint-Éloi, 80, avenue Augustin-Fliche, 34295 Montpellier Cedex 5

The human immunodeficiency virus type 1 (HIV-1) uses, in addition to the CD4 molecule, a chemokine receptor as a receptor to infect T lymphocytes. Most viral strains use the chemokine receptor CCR5 as a coreceptor. The density of CCR5 molecules on CD4+ T cells varies widely among individuals, but is constant over time for a given individual. Infected subjects with high CCR5 expression present high viral load, progress rapidly, respond poorly to antiretroviral therapies, and have high viral rebond after treatment interruption. This is due to the fact that in cells expressing high surface CCR5 densities, the binding of the virus to its coreceptor triggers strong activation signals, that transit through Gαi proteins, and facilitate the reverse transcription of the viral RNA. Thus, CCR5 is not only a dock for HIV-1 but also a choke preparing the target cell to replicate the virus. This model could explain intercellular variabilities in infectibility by differences in the capacity of the virus to activate the cell it infects. Moreover, this model opens new therapeutic opportunities targeting the pathways activated by the virus for his advantage.