The Ambiguous Roles of Extracellular Vesicles in HIV Replication and Pathogenesis

Abstract

Cells from all kingdoms of life can release membrane-enclosed vesicles to the extracellular milieu. These extracellular vesicles (EVs) may function as mediators of intercellular communication, allowing the transfer of biologically active molecules between cells and organisms. It has become clear that HIV particles and certain types of EVs, such as exosomes, share many similarities regarding morphology, composition, and biogenesis. This review presents a summary of the literature describing the intricate relationship between HIV and EVs biogenesis. Also, we discuss the latest progress toward understanding the mechanisms by which EVs influence HIV pathogenesis, as well as, how HIV modulates EVs composition in infected cells to facilitate viral spread.

Inclusion Biogenesis, Methods of Isolation and Clinical Application of Human Cellular Exosomes

“…Tang et al recently engineered exosomal Tat to specifically reactivate latent human immunodeficiency virus 1 (HIV-1) [96]. Further, CD4+ exosomes released from CD4+ T cells seem to hinder spread of HIV virus by competing with viral particles in terms of binding to other molecules and therefore restrict viral replication by for example delivering active molecules [97]. Currently, it is clear that exosomes also are vehicles for HIV particles in acquired immune deficiency syndrome (AIDS) infected persons, contributing to the overall pathogenic effect.…”

Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

“…Constituents within the culture medium or serum/plasma samples are separated based on the isodensity zones formed during ultracentrifugation for density gradient-based EV isolation. The samples are layered on top of the density-gradient solution and ultracentrifuged at 10,000× g. This ultracentrifugation separates exosomes from the other sample constituents based on density and size Whiteside TL [ 17 , 18 , 19 ] 2018, Kamerkar S et al [ 17 , 18 , 19 ] 2017, Lobb RJ et al [ 17 , 18 , 19 ] 2015. The most commonly used solution for this method is either iodixanol (OptiPrep™ STEMCELL Technologies, Vancouver, BC, Canada) or a 30% sucrose solution.…”

“…Inhibition of either RAB35 or RAB11 impaired exosome secretion in cells bearing the proteolipid protein (PLP) exosome biomarker or the heat shock cognate (Hsc70) chaperone protein, respectively [ 15 , 16 ]. Additionally, the absence of RAB2B, RAB51, RAB9A, RAB27A, or RAB27B in HeLa cells, via knock-out, results in exosome secretion inhibition demonstrating that these RAB GTPases are required for exosome biogenesis [ 17 , 18 ]. Exosome biogenesis and autophagy have an inverse relationship [ 18 , 19 ].…”

Exosomes in Bone Sarcomas: Key Players in Metastasis

“…For instance, they play important roles in immune response and surveillance [34], neurotransmitter release by neurons [35], or tissue repair [36]. Similarly, cells use exosomes under pathological conditions, such as virus infections and spread [37] or cancer [7]. Furthermore, from a clinical point of view, exosomes and their cargo could be exploited as circulating biomarkers due to the ability to correlate their profile to the cell of origin [38].…”