11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11:abstract no. 45

Quentin J Sattentau and C Jolly
The Sir William Dunn Sch of Pathology, Univ of Oxford, UK

BACKGROUND: HIV-1 can spread both by release of cell-free virions and by direct cell-cell spread. Cell-cell spread has advantages for the virus including production of new viral RNA and proteins that is more rapid than that observed after cell-free virus infection, and potential escape from elements of humoral immunity. We have established a model system, based on conjugate formation between HIV-1-infected (effector) T cells and uninfected (target) primary CD4+ T cells, to analyze the molecular events taking place during cell-cell spread.

RESULTS: We demonstrate that conjugate formation induces rapid, actin-dependent recruitment to the interface of CD4, CXCR4, and LFA-1 on the target cell, and Env and Gag on the effector cell. We have termed this adhesive junction formed between the effector and target cells a "virological synapse," by analogy with the synapse recently described for cell-cell spread of HTLV-1. Formation of the HIV-1 synapse is coordinate with transfer of viral Gag across the synaptic space into the target cell, a process that probably takes place via directed fusion of virions with the target cell membrane.

CONCLUSIONS: Preliminary results suggest that the synaptic junction is elaborated via signaling cascades initiated by Env engagement of CXCR4, and that Env may signal into the effector cell to recruit Gag to the synapse.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.