Abstract
The human immunodeficiency virus (HIV-1) disseminates in the body and is found in several organs and tissues. Although HIV-1 mainly targets both CD4+ T lymphocytes and macrophages, it has contrasting effects between these cell populations. HIV-1 infection namely reduces the viability of CD4+ T cells, whereas infected macrophages are long-lived. In addition, the migration of T cells is reduced by the infection, whereas HIV-1 differentially modulates the migration modes of macrophages. In 2-dimensions (2D) assays, infected macrophages are less motile compared to the control counterparts. In 3D environments, macrophages use two migration modes that are dependent on the matrix architecture: amoeboid and mesenchymal migration. HIV-1-infected macrophages exhibit a reduced amoeboid migration but an enhanced mesenchymal migration, via the viral protein Nef. Indeed, the mesenchymal migration involves podosomes, and Nef stabilizes these cell structures through the activation of the tyrosine kinase Hck, which in turn phosphorylates the Wiskott–Aldrich syndrome protein (WASP). WASP is a key player in actin remodeling and cell migration. The reprogramed motility of infected macrophages observed in vitro correlates in vivo with enhanced macrophage infiltration in experimental tumors in Nef-transgenic mice compared to control mice. In conclusion, HIV infection of host target cells modifies their migration capacity; we infer that HIV-1 enhances virus spreading in confined environments by reducing T cells migration, and facilitates virus dissemination into different organs and tissues of the human body by enhancing macrophage mesenchymal migration.
Highlights
The biology and pathogenesis of HIV infection has been largely studied since the discovery of the virus in 1983
We have recently shown that macrophage migration is reprogramed on infection [8], a mechanism that could contribute to HIV-1 dissemination in the body
Despite the fact that HIV-1 or HIV-1 proteins are well known to induce a “bystander” effect on macrophage migration through the concerted modulation of cytokines/chemokines [9,10,11,12,13]; in this review, we focus on the intracellular molecular impact of HIV-1 to control the migration of host cells
Summary
The biology and pathogenesis of HIV infection has been largely studied since the discovery of the virus in 1983. Regarding HIV-infected T cells, they are able to migrate within lymph nodes favoring virus spreading by a cell-to-cell transfer mechanism [7]. The migration of CD4+ T lymphocytes is inhibited by HIV-1 infection both in vitro and in lymph nodes [7, 14,15,16,17,18]. The HIV1 protein Nef is responsible for the inhibition of T cell migration in vitro both in 2D and in 3D environments [14,15,16,17,18].
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