Exosomes Decrease In Vitro Infectivity of HIV-1 Preparations: Implication for CD4+T Lymphocyte Depletion In Vivo

Abstract

1.1 Nature and role of exosomes Since their identification by Johnstone et al (Johnstone et al., 1987), exosomes have gained importance in understanding many biological processes. Exosomes are vesicles expelled by cells into the extracellular milieu. They originate from internal endocytic compartments called multivesicular bodies (MVB) and are released following fusion of MVB with the plasma membrane (Stoorvogel et al., 2002). Numerous cell types, including tumour, foetal, epithelial and haematopoietic cells share the characteristics of releasing exosomes upon activation by cytokines (Abusamra et al., 2005; Ahn and Johnstone, 1993; Altieri, Khan, and Tomasi, 2004; Peche et al., 2006; Segura, Amigorena, and Thery, 2005; Taylor, Akyol, and Gercel-Taylor, 2006; van Niel and Heyman, 2002). Initially associated with the elimination of obsolete proteins during reticulocyte maturation, exosomes are now known to play several roles in intercellular communication (for reviews, (Chaput and Thery, 2010) and (Record et al., 2011)). Based on the presence of various molecules within the vesicle membrane or lumen, it has been proposed that exosomes are particularly involved in regulation of the immune response, for example tolerance induction (Admyre et al., 2006; Frangsmyr et al., 2005; Kapsogeorgou et al., 2005; Karlsson et al., 2001; Kim, Morse, and Choi, 2006; Larregina et al., 2004; Mallegol, van Niel, and Heyman, 2005; Ostman, Taube, and Telemo, 2005; Peche et al., 2003; Peche et al., 2006; Quah and O'Neill, 2005a; Segura, Amigorena, and Thery, 2005; Taylor, Akyol, and GercelTaylor, 2006; Van Niel et al., 2003), antigen presentation (Andre et al., 2004; Chaput et al., 2004; Clayton et al., 2003; Kleijmeer et al., 2001; Peche et al., 2003; Raposo et al., 1996; Thery et al., 2002), cancer immunotherapy (Amigorena, 2000; Andre et al., 2001; Mignot et al., 2006; Quah and O'Neill, 2000; Zitvogel et al., 1998), control of receptor expression (Ahn and Johnstone, 1993; Hawari et al., 2004; Levine, 2004), mechanisms involved in cell death (Abusamra et al., 2005; Farsad, 2002; Iero et al., 2008; Lenassi et al., 2010; Zhang et al., 2006) and control of inflammation (Abusamra et al., 2005; Kim et al., 2006; Levine, 2004). Exosomes may also contain functional miRNA (Pegtel et al., 2010) or deliver bioactive lipids (Esser et al., 2010; Subra et al., 2010). Depending on the function and on