14th International AIDS Conference Barcelona, Spain — July 7-12, 2002

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. A10002

BACKGROUND: Infection of CD4+ T lymphocytes by HIV is responsible for the gradual loss of immune function which leads to AIDS. Yet, HIV is not only found in CD4+ T cells that actively produce virus but also in quiescent naïve and memory lymphocytes in which it creates a stable reservoir of its genetic material. This reservoir lasts for years and is resistant to treatment by highly active anti-retroviral therapy, thus creating a permanent obstacle to eradication of virus from the patient. Infection of resting lymphocytes by HIV seems paradoxical as the great majority of resting lymphocytes do not express detectable levels of the viral receptor CCR5.

METHODS: We developed a highly sensitive method which measures exclusively the HIV entry step, that is the envelope-mediated membrane fusion. This assay, named FLASH (Fluorescence-based Assay of Syncytia induced by HIV envelope) is based on cytoplasmic fluorescent dye transfer after viral envelope-mediated fusion of cells.

RESULTS: We were able to show that CCR5 receptor is undetectable at the cell surface of resting lymphocytes by FACS analysis. Paradoxically resting cells HIV allow envelope-mediated membrane fusion. Fusion proceeds unambiguously via CD4 and CCR5 receptors as lymphocytes from donors carrying a deletion in the CCR5 gene are resistant.

CONCLUSIONS: We conclude that minute amounts of funtional CCR5 are present on resting CD4+ T cells. HIV has the capacity to exploit very low levels of the CCR5 receptor to directly enter CD4+ T lymphocytes ultimately leading to the creation of a treatment-resistant reservoir of latently infected cells.

Presenting author: Ralf Altmeyer

1Institut Pasteur, Paris, France.

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