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Retrovirology 2008
HIV transfer between CD4 T cells does not require LFA-1 binding to ICAM-1 and is governed by the interaction of HIV envelope glycoprotein with CD4Abstract: The formation of cellular conjugates and subsequent HIV transmission between productively infected MOLT cell lines and primary CD4 T cells was not inhibited by a panel of blocking antibodies against ICAM-1, ICAM-3 and α and β chains of LFA-1. Complete abrogation of HIV transmission and formation of cellular conjugates was only observed when gp120/CD4 interactions were blocked. The dispensable role of LFA-1 in HIV transmission was confirmed using non-lymphoid 293T cells, lacking the expression of adhesion molecules, as HIV producing cells. Moreover, HIV transmission between infected and uninfected primary CD4 T cells was abrogated by inhibitors of gp120 binding to CD4 but was not inhibited by blocking LFA-1 binding to ICAM-1 or ICAM-3. Rather, LFA-1 and ICAM-3 mAbs enhanced HIV transfer. All HIV producing cells (including 293T cells) transferred HIV particles more efficiently to memory than to naive CD4 T cells.In contrast to other mechanisms of viral spread, HIV transmission between infected and uninfected T cells efficiently occurs in the absence of adhesion molecules. Thus, gp120/CD4 interactions are the main driving force of the formation of cellular contacts between infected and uninfected CD4 T cells whereby HIV transmission occurs.Cell-to-cell HIV transmission is a major determinant of HIV spread in vivo [1] and is required for efficient HIV replication in vitro [2]. Although free HIV particles are infectious, they show a short lifespan at 37°C [3] and lower infectivity than cell-to-cell HIV transmission [4]. Cell-to-cell virus transmission occurs through the formation of stable cellular contacts defined as virological synapses [5], that can be formed between a target CD4 T cell and either a dendritic cell (DC) or a productively HIV infected cell. Although both synapses share the common function of transmitting HIV to CD4 T cells, their structures appreciably differ: DC-T cell synapses concentrate TCR/MHC complexes in the central supramolecular activation clus
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