The accumulation of macrophages in tissues such as the kidneys, liver and intestine has been reported during infection with HIV-1 and simian immunodeficiency virus. In Blood, Maridonneau-Parini and colleagues investigate the mechanistic basis of altered macrophage distribution during HIV-1 infection. Using in vitro models of macrophage migration, they find that HIV-1 infection selectively increases the mesenchymal mode of macrophage migration at the expense of amoeboid movement. This is relevant to tissue invasiveness because mesenchymal migration is characterized by podosomes and is proteolytic, which allows penetration of substrates with low porosity. Adoption of the mesenchymal mode depends on HIV-1's expression of functional negative factor protein (Nef). Indeed, mice with transgenic expression of Nef show a proclivity for mesenchymal macrophage migration as well as enrichment for macrophages in tissues or implanted tumors. Nef operates by activating a Hck-WASP–mediated pathway required for the formation and stability of podosomes. These findings suggest that Nef-triggered redistribution of macrophages to tissues might therefore contribute to the dissemination of HIV-1 and pathogenesis of AIDS.

Blood 125, 1611–1622 (2015)