Richard L. Felts,
Kedar Narayan,
Jacob D. Estes,
Dan Shi,
Charles M. Trubey,
Jing Fu,
Lisa M. Hartnell,
Gordon T. Ruthel,
Douglas K. Schneider,
Kunio Nagashima,
Julian W. Bess Jr,
Sina Bavari,
Bradley C. Lowekamp,
Donald Bliss,
Jeffrey D. Lifson,
Sriram Subramaniam
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ABSTRACT: The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4+ T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known
as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed
the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature
dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived
from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial
extensions emanating from CD4+ T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic
cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively
at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells
from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer
by T cells highlight unique aspects of cell-cell HIV transmission.
Proceedings of the National Academy of Sciences 07/2010; 107(30):13336-13341. · 9.68 Impact Factor
