 |
45
HIV-1 Spread between T Cells via a Virological Synapse
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.
|
