Semen exosomes (SE) from HIV-uninfected (HIV-) individuals potently inhibit
HIV infection in vitro. However, morphological changes in target cells in response to SE have not been characterized or have the effect of
HIV infection or the use of illicit substances, specifically psychostimulants, on the function of SE been elucidated. The objective of this study was to evaluate the effect of
HIV infection, psychostimulant use, and both together on SE-mediated regulation of monocyte function. SE were isolated from semen of HIV- and HIV-infected (HIV+) antiretroviral
therapy (ART)-naive participants who reported either using or not using psychostimulants. The SE samples were thus designated as HIV-Drug-, HIV-Drug+, HIV+Drug-, and HIV+Drug+. U937 monocytes were treated with different SEs and analyzed for changes in transcriptome, morphometrics, actin reorganization, adhesion, and chemotaxis.
HIV infection and/or use of psychostimulants had minimal effects on the physical characteristics of SE. However, different SEs had diverse effects on the
messenger RNA signature of monocytes and rapidly induced monocyte adhesion and spreading. SE from HIV infected or psychostimulants users but not HIV-Drug- SE, stimulated actin reorganization, leading to the formation of filopodia-like structures and membrane ruffles containing
F-actin and
vinculin that in some cases were colocalized. All SE stimulated monocyte chemotaxis to HIV secretome and activated the secretion of
matrix metalloproteinases, a phenotype exacerbated by
HIV infection and psychostimulant use. SE-directed regulation of cellular morphometrics and chemotaxis depended on the donor clinical status because
HIV infection and psychostimulant use altered SE function. Although our inclusion criteria specified the use of
cocaine, humans are poly-drug and alcohol users and our study participants used psychostimulants, marijuana,
opiates, and alcohol. Thus, it is possible that the effects observed in this study may be due to one of these other substances or due to an interaction between different substances.