Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities

Kaddour, Hussein; Lyu, Yuan; Welch, Jennifer L.; Paromov, Victor; Mandape, Sammed N.; Sakhare, Shruti S.; Pandhare, Jui; Stapleton, Jack T.; Pratap, Siddharth; Dash, Chandravanu; Okeoma, Chioma M.

doi:10.1074/mcp.ra119.001594

Cited by 28 publications

(38 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To gain insight into the differential response of BEVs and SEVs to neuraminidase, we performed a secondary analysis of our previously published Kaddour et al, proteomics dataset of BEVs and SEVs isolated from uninfected or HIV-infected ART-suppressed individuals [ 51 ]. The Kaddour et al, study identified 218 and 246 differentially present proteins (DPPs) in SEV as compared to BEVs in HIV- and HIV+ groups, respectively.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Electrostatic Surface Properties of Blood and Semen Extracellular Vesicles: Implications of Sialylation and HIV-Induced Changes on EV Internalization

Kaddour

Panzner

Welch

et al. 2020

Viruses

Self Cite

View full text Add to dashboard Cite

Although extracellular vesicle (EV) surface electrostatic properties (measured as zeta potential, ζ-potential) have been reported by many investigators, the biophysical implications of charge and EV origin remains uncertain. Here, we compared the ζ-potential of human blood EVs (BEVs) and semen EVs (SEVs) from 26 donors that were HIV-infected (HIV+, n = 13) or HIV uninfected (HIV-, n = 13). We found that, compared to BEVs that bear neutral surface charge, SEVs were significantly more negatively charged, even when BEVs and SEVs were from the same individual. Comparison of BEVs and SEVs from HIV- and HIV+ groups revealed subtle HIV-induced alteration in the ζ-potential of EVs, with the effect being more significant in SEVs (∆ζ-potential = −8.82 mV, p-value = 0.0062) than BEVs (∆ζ-potential = −1.4 mV, p-value = 0.0462). These observations were validated by differences in the isoelectric point (IEP) of EVs, which was in the order of HIV + SEV ≤ HIV-SEV ≪ HIV + BEV ≤ HIV-BEV. Functionally, the rate and efficiency of SEV internalization by the human cervical epithelial cell line, primary peripheral blood lymphocytes, and primary blood-derived monocytes were significantly higher than those of BEVs. Mechanistically, removal of sialic acids from the surface of EVs using neuraminidase treatment significantly decreased SEV’s surface charge, concomitant with a substantial reduction in SEV’s internalization. The neuraminidase effect was independent of HIV infection and insignificant for BEVs. Finally, these results were corroborated by enrichment of glycoproteins in SEVs versus BEVs. Taken together, these findings uncover fundamental tissue-specific differences in surface electrostatic properties of EVs and highlight the critical role of surface charge in EV/target cell interactions.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Represented data are an average of 16 fields of view per well and 6 wells per treatment. ( e ) Venn diagram between the differentially present proteins (DPPs) enriched in SEVs as compared to BEV from the HIV- and HIV+ groups, as analyzed in [ 51 ]. ( f ) Heatmap clustering analysis of the 21 glycocalyx-related SEV-enriched DPPs (rows).…”

Section: Resultsmentioning

confidence: 99%

Electrostatic Surface Properties of Blood and Semen Extracellular Vesicles: Implications of Sialylation and HIV-Induced Changes on EV Internalization

Kaddour

Panzner

Welch

et al. 2020

Viruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have previously used different isolation protocols to purify EVs from both human semen and blood [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 44 ] and, recently, we optimized the isolation protocol that utilized a size-guided chromatographic technique to purify EVs from all body fluids [ 42 ]. We used this protocol to purify EVs from blood to gain novel insights into the effect of SIV infection and THC treatment on BEV size and concentration.…”

Section: Resultsmentioning

confidence: 99%

“…Further, there is a significant knowledge gap in the contribution of extracellular vesicles (EVs) to the effects of THC in the setting of HIV/SIV infection. EVs are a key player in the pathogenesis of viral infections [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. EVs are cargo-carrying, quasi-nanovesicles that mediate distal and proximal intercellular communications [ 45 , 46 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is also reasonable to assume that cannabinoid signaling is present in cells that produce EVs and that cannabinoids may mediate their effects via EVs since all eukaryotic cells release EVs [ 60 , 61 ]. It has previously been shown that EVs were detected in the blood of RMs and humans infected with SIV [ 62 ] or HIV [ 34 , 38 ]. However, the longitudinal effect of HIV/SIV infection on EV release, cargo, and function is lacking.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long-Term Low-Dose Delta-9-Tetrahydrocannbinol (THC) Administration to Simian Immunodeficiency Virus (SIV) Infected Rhesus Macaques Stimulates the Release of Bioactive Blood Extracellular Vesicles (EVs) that Induce Divergent Structural Adaptations and Signaling Cues

Lyu

Kopcho

Mohan

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

Blood extracellular vesicles (BEVs) carry bioactive cargo (proteins, genetic materials, lipids, licit, and illicit drugs) that regulate diverse functions in target cells. The cannabinoid drug delta-9-tetrahydrocannabinol (THC) is FDA approved for the treatment of anorexia and weight loss in people living with HIV. However, the effect of THC on BEV characteristics in the setting of HIV/SIV infection needs to be determined. Here, we used the SIV-infected rhesus macaque model of AIDS to evaluate the longitudinal effects of THC (THC/SIV) or vehicle (VEH/SIV) treatment in HIV/SIV infection on the properties of BEVs. While BEV concentrations increased longitudinally (pre-SIV (0), 30, and 150 days post-SIV infection (DPI)) in VEH/SIV macaques, the opposite trend was observed with THC/SIV macaques. SIV infection altered BEV membrane properties and cargo composition late in infection, since i) the electrostatic surface properties (zeta potential, ζ potential) showed that RM BEVs carried negative surface charge, but at 150 DPI, SIV infection significantly changed BEV ζ potential; ii) BEVs from the VEH/SIV group altered tetraspanin CD9 and CD81 levels compared to the THC/SIV group. Furthermore, VEH/SIV and THC/SIV BEVs mediated divergent changes in monocyte gene expression, morphometrics, signaling, and function. These include altered tetraspanin and integrin β1 expression; altered levels and distribution of polymerized actin, FAK/pY397 FAK, pERK1/2, cleaved caspase 3, proapoptotic Bid and truncated tBid; and altered adhesion of monocytes to collagen I. These data indicate that HIV/SIV infection and THC treatment result in the release of bioactive BEVs with potential to induce distinct structural adaptations and signaling cues to instruct divergent cellular responses to infection.

show abstract

Exosome Processing and Characterization Approaches for Research and Technology Development

et al. 2022

View full text Add to dashboard Cite

Exosomes are extracellular vesicles that share components of their parent cells and are attractive in biotechnology and biomedical research as potential disease biomarkers as well as therapeutic agents. Crucial to realizing this potential is the ability to manufacture high‐quality exosomes; however, unlike biologics such as proteins, exosomes lack standardized Good Manufacturing Practices for their processing and characterization. Furthermore, there is a lack of well‐characterized reference exosome materials to aid in selection of methods for exosome isolation, purification, and analysis. This review informs exosome research and technology development by comparing exosome processing and characterization methods and recommending exosome workflows. This review also provides a detailed introduction to exosomes, including their physical and chemical properties, roles in normal biological processes and in disease progression, and summarizes some of the on‐going clinical trials.

show abstract

Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities

Cited by 28 publications

References 92 publications

Electrostatic Surface Properties of Blood and Semen Extracellular Vesicles: Implications of Sialylation and HIV-Induced Changes on EV Internalization

Electrostatic Surface Properties of Blood and Semen Extracellular Vesicles: Implications of Sialylation and HIV-Induced Changes on EV Internalization

Long-Term Low-Dose Delta-9-Tetrahydrocannbinol (THC) Administration to Simian Immunodeficiency Virus (SIV) Infected Rhesus Macaques Stimulates the Release of Bioactive Blood Extracellular Vesicles (EVs) that Induce Divergent Structural Adaptations and Signaling Cues

Exosome Processing and Characterization Approaches for Research and Technology Development

Contact Info

Product

Resources

About