Mechanisms of HIV-1 cell-to-cell transfer to myeloid cells

Abstract

In addition to CD4+ T lymphocytes, cells of the myeloid lineage such as macrophages, dendritic cells (DCs), and osteoclasts (OCs) are emerging as important target cells for HIV‐1, as they likely participate in all steps of pathogenesis, including sexual transmission and early virus dissemination in both lymphoid and nonlymphoid tissues where they can constitute persistent virus reservoirs. At least in vitro, these myeloid cells are poorly infected by cell‐free viral particles. In contrast, intercellular virus transmission through direct cell‐to‐cell contacts may be a predominant mode of virus propagation in vivo leading to productive infection of these myeloid target cells. HIV‐1 cell‐to‐cell transfer between CD4+ T cells mainly through the formation of the virologic synapse, or from infected macrophages or dendritic cells to CD4+ T cell targets, have been extensively described in vitro. Recent reports demonstrate that myeloid cells can be also productively infected through virus homotypic or heterotypic cell‐to‐cell transfer between macrophages or from virus‐donor‐infected CD4+ T cells, respectively. These modes of infection of myeloid target cells lead to very efficient spreading in these poorly susceptible cell types. Thus, the goal of this review is to give an overview of the different mechanisms reported in the literature for cell‐to‐cell transfer and spreading of HIV‐1 in myeloid cells.

Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection

“…2A). While HIV-1 infection with cell-free viral particles has been largely documented, the virus may also be transmitted by direct cell-to-cell contacts ( 43 , 44 ). Thus, we further analyzed whether spermine may inhibit cell-to-cell transfer of X4 and R5 primary HIV-1 strains from infected T cells to noninfected CD4 + T cells or monocyte-derived macrophages.…”

CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments

“…Also, the cellular environment generated after macrophage infection with lab-adapted or T/F HIV strains can enhance infection of resting CD4+ T cells (19) and can even skew the differentiation of activated CD4+ T cells into more permissive profiles (20). Vice versa, it is well established that HIV-1 infected CD4+ T cells transmit HIV-1 to macrophages through the virological synapse, direct cell-to-cell contact and even via phagocytosis and fusion with infected CD4+ T cells (56,(58)(59)(60).…”

Tunneling nanotubes and tumor microtubes—Emerging data on their roles in intercellular communication and pathophysiology: Summary of an International FASEB Catalyst Conference October 2023

“…It has been accepted that viral reactivation under ART depends on the random soluble cellfree virus to reach uninfected cells. [62][63][64][65][66] However, in vitro, in vivo, and in silico experiments or models cannot explain the biological data. [67][68][69][70][71][72][73][74][75][76] To address this knowledge gap, several groups identified the virological synapses, VS, as an alternative mechanism of targeted infection mediated by cell-to-cell communication, dependent on adhesion molecules and localized viral budding, but not on viral diffusion.…”

“…Nevertheless, the mechanisms of viral spread during the early stages of infection and reactivation, where the soluble virus is low to undetectable, are poorly described. It has been accepted that viral reactivation under ART depends on the random soluble cell‐free virus to reach uninfected cells 62–66 . However, in vitro, in vivo, and in silico experiments or models cannot explain the biological data 67–76 .…”