Fig. 7.

Pathways of macrophage intra- and intercellular HIV-1 trafficking. HIV-1 receptor-mediated entry is regulated by clathrin-coated pits (Miyauchi et al. 2009). Upon inhibition of dynamin by dynasore, viral entry is blocked. Clathrin-coated vesicles containing HIV-1 may undergo Rab5/EEA1-dependant fusion with the early sorting endosome(Bucci et al. 1992; Zerial and McBride 2001). Endosomes can pinch off the vesiculo-tubular network also termed early sorting endosome (Maxfield and McGraw 2004) and undergo the following downstream sorting routes: a fuse with the endocytic recycling compartment (ERC; perinuclear region) and then undergo Tfn-like Rab11-mediated recycling to the BC and plasma membrane (Maxfield and McGraw 2004). Disruption of this processes by brefeldin A results in accumulation of HIV-1 constituents in large cytosolic compartments (Wang et al. 2001). b undergo sorting to the MVB for ILV biogenesis, virus assembly and budding regulated by ESCRT family (Babst et al. 2002; Garrus et al. 2001; Gill et al. 2007). MVB in turn may undergo fusion with Rab11 endosomes to be transported either to the plasma membrane for exosomal release (Simons and Raposo 2009) or intercellular transfer through the conduits. Disruption of MVB biogenesis by wortmannin results in agregation of HIV-1 constituents in large vaccuoles (Gruenberg and Stenmark 2004). Lysosomes may undergo backfusion with MBV and Rab11 compartments to be targeted at the plasma membrane (secretory non-degrading lysosomes; (Blott and Griffiths 2002; Luzio et al. 2005) or the bridging conduits. In parallel to endocytic entry and intercellular trafficking, virion-plasma membrane fusion may also occur followed by uncoating, reverse trancription, formation of pre-integration complexes (PIC), and RNA expression (Brass et al. 2008). Thick blue arrows indicate trafficking routes that target HIV-1 directly to the conduits