Abstract
While HIV-1 infection of target cells with cell-free viral particles has been largely documented, intercellular transmission through direct cell-to-cell contact may be a predominant mode of propagation in host. To spread, HIV-1 infects cells of the immune system and takes advantage of their specific particularities and functions. Subversion of intercellular communication allows to improve HIV-1 replication through a multiplicity of intercellular structures and membrane protrusions, like tunneling nanotubes, filopodia, or lamellipodia-like structures involved in the formation of the virological synapse. Other features of immune cells, like the immunological synapse or the phagocytosis of infected cells are hijacked by HIV-1 and used as gateways to infect target cells. Finally, HIV-1 reuses its fusogenic capacity to provoke fusion between infected donor cells and target cells, and to form infected syncytia with high capacity of viral production and improved capacities of motility or survival. All these modes of cell-to-cell transfer are now considered as viral mechanisms to escape immune system and antiretroviral therapies, and could be involved in the establishment of persistent virus reservoirs in different host tissues.
Highlights
Specialty section: This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology
While HIV-1 was initially suspected to enter its target cells only through fusion of viral particles with host T-cell membranes, it appears more and more evident that it can use a large diversity of cellular features to infect target cells, especially through direct cell-to-cell transmission by close contacts between an infected virus-donor cell and a target cell
Cell-to-cell transfer of HIV-1 allows a massive release of viral material toward the target cell inducing a strong increase of viral infectivity, compared with infection with cell-free viruses
Summary
The formation of the so-called virological synapse is the major and well-established route for viral cell-to-cell transmission, and was first described in the context of human T-lympho-tropic virus infection as a close and organized cell-to-cell contact structure between an infected donor cell and a target cell, enabling the transfer of viral material between the two cells [41] (Figure 1D). The virological synapse is a dynamic structure initiated by the recognition of the target T-cell surface receptor CD4 by the viral surface envelope glycoprotein gp120 expressed at the surface of the infected donor T cell (Figure 2) This interaction allows the recruitment of the viral Gag polyprotein precursor to the intercellular interface [52] and triggers the recruitment of co-receptors, CXCR4 or CCR5, adhesion molecules LFA-1, ICAM-1, and other cell surface proteins such as tetraspanins to the site of intercellular contact, for stabilization of the virological synapse and efficient viral transfer [48, 52, 53]. This effect of protease inhibitors compared with reverse transcriptase inhibitors is suspected to be due to their ability to target immature virions and blocking their maturation in fully infectious viruses It seems from the data reported in the literature that the idea that the cell-to-cell viral transfer through the virological synapse can escape from neutralizing antibodies and antiretroviral drugs is not so evident and is probably dependent on the inhibitors used.
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