Mechanisms for Cell-to-Cell Transmission of HIV-1

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.

Keywords: HIV-1; T cells; cell-to-cell transfer; dendritic cells; macrophages.

Figure 1

Intercellular structures and processes involved in cell-to-cell transmission of HIV-1. (A–G) Schemes represent the different pathways for HIV-1 cell-to-cell transfer between donor cells (in green) and target cells (in pink).

Figure 2

Models for HIV-1 entry downstream of the virological synapse. After budding and release from infected donor cells, HIV could be able to enter the target cells via two distinct pathways. (left) Entry through endocytic pathway: immature virions interact with the CD4 receptor at cell surface of target cell, are internalized by endocytosis, mature in endocytic compartments, and fuse with the luminal membrane of endosomes. (right) Fusion with plasma membrane: mature viruses are captured by CD4, at the surface of target cells, and directly fuse with plasma membrane for release of viral material in the cytoplasm of the target cells.