Macrophages and HIV-1: An Unhealthy Constellation

Abstract

Lentiviruses have a long-documented association with macrophages. Abundant evidence exists for in vitro and, in a tissue-specific manner, in vivo infection of macrophages by the primate lentiviruses HIV-1 and SIV. However, macrophage contribution to aspects of HIV-1 and SIV pathogenesis, and their role in viral persistence in individuals on suppressive antiretroviral therapy, remains unclear. Here we discuss recent evidence implicating macrophages in HIV-1-mediated disease and highlight directions for further investigation.

Keywords: HIV-1; macrophage; pathogenesis; reservoir.

Figure 1. In vitro models of macrophage exposure to HIV-1-infected T cells

CD4⁺ T cells infected by cell-free HIV-1 (A) or by cell-cell spread from macrophages that are infected or have captured HIV-1 (B) may be engulfed by uninfected macrophages (C). (D) Shows an Imagestream® image of a macrophage that has engulfed multiple Gag⁺ Caspase-3⁺ T cells. This may result in macrophage infection as evidenced by extensive macrophage cytoplasmic Gag label after coculture of infected T cells with macrophages (E), or false positive infection (F) in which the infection does not pass from the T cell to the macrophage, in this case because the macrophage is treated with AZT. Imagestream® images (D, E, F) were obtained by A. Baxter.

Figure 2. The VCC in an in vitro infected macrophage

A monocyte-derived macrophage infected in vitro and labeled for CD4 (green) shows individual virions labeled for Gag (red) within the virus-containing compartment at low magnification by confocal microscopy (box, bar = 2.5 μm) and high magnification by stimulated emission-depletion (STED) super-resolution fluorescence microscopy (main figure, bar = 400nm). Sample prepared by T. Do and images acquired by J. Chojnaki.