Human immunodeficiency virus type 1 entry into macrophages mediated by macropinocytosis

Whereas human inmmunodeficiency virus (HIV) infects various cell types by f usion at the plasma membrane, we observed a different entry route in human primary macrophages, in which macropinocytosis is active. Shortly after exp osure of macrophages to HIV-1 and irrespective of viral envelope-receptor i nteractions, particles were visible in intracellular vesicles, which were i dentified as macropinosomes. Most virions appeared subsequently degraded. H owever, fusion leading to capsid release in the cytosol and productive infe ction could take. place inside vesicles when particles were properly envelo ped. These observations provide new insights into HIV-1 interactions with a cell target relevant to pathogenesis. They may have implications for the d esign of soluble inhibitors aimed at interfering with the fusion or entry p rocesses.