Human immunodeficiency virus type 1 induces cellular polarization, intercellular adhesion molecule-1 redistribution, and multinucleated giant cell generation in human primary monocytes but not in monocyte-derived macrophages.

In this study, we evaluated the effects of human immunodeficiency virus type 1 (HIV-1) on some morphologic and functional changes in cultured human monocytes/macrophages at different stages of differentiation. Freshly isolated monocytes infected with HIV-1 24 hours after seeding exhibited marked morphologic changes such as uropod formation, polarization of intercellular adhesion molecule-1 (ICAM-1) on the cytoplasmic projection, the redistribution of alpha-actinin on cell-membrane dots, and an increased release of soluble ICAM-1. These changes preceded the increase in monocyte-monocyte fusion and the formation of multinucleated giant cells. In contrast, HIV-1 infection did not affect monocyte-derived macrophages in terms of either cellular polarization or multinucleated giant cell formation. Immunocytochemistry showed that HIV-1 matrix protein was present mostly in bi- and trinucleated cells, which suggests that multinucleated giant cells may represent a long-lived and highly productive cellular source of HIV. The treatment of the HIV-1-infected monocytes with azidodeoxythymidine virtually abolished all viral-induced morphofunctional changes. On the whole, these results indicate that blood monocytes and differentiated macrophages may be affected differently by HIV infection, as monocytes seem to be much more prone to polarize, undergo homotypic fusion, and form multinucleated giant cells. These changes may confer to HIV-infected monocytes an increased ability to transmigrate through endothelia into tissues, whereas differentiated macrophages may have a predominant role as a widespread reservoir of HIV.