Protein cargo of Nef-containing exosomal extracellular vesicles may predict HIV-associated Neurocognitive Impairment status.

Autor:	Caobi A; Herbert Wertheim College of Medicine at Florida International University, Department of Immunology and Nanomedicine, Miami, 33199, USA., Werne R; Herbert Wertheim College of Medicine at Florida International University, Department of Immunology and Nanomedicine, Miami, 33199, USA., Gomez M; College of Arts, Sciences, and Education at Florida International University; Department of Chemistry and Biochemistry; Advanced Mass Spectrometry Facility, Miami, FL 33199., Andre M; Herbert Wertheim College of Medicine at Florida International University, Department of Immunology and Nanomedicine, Miami, 33199, USA., Thomas C; Herbert Wertheim College of Medicine at Florida International University, Department of Immunology and Nanomedicine, Miami, 33199, USA., Yndart A; Herbert Wertheim College of Medicine at Florida International University, Department of Immunology and Nanomedicine, Miami, 33199, USA., Lima-Hernandez F; College of Arts, Sciences, and Education at Florida International University; Department of Chemistry and Biochemistry; Advanced Mass Spectrometry Facility, Miami, FL 33199., Nair M; Herbert Wertheim College of Medicine at Florida International University, Department of Immunology and Nanomedicine, Miami, 33199, USA., Raymond AD; Herbert Wertheim College of Medicine at Florida International University, Department of Immunology and Nanomedicine, Miami, 33199, USA.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Jun 23. Date of Electronic Publication: 2023 Jun 23.
DOI:	10.21203/rs.3.rs-2740135/v2
Abstrakt:	Exosomal extracellular vesicles (xEVs) in plasma and cerebrospinal fluid (CSF) of aviremic people living with HIV/AIDS (PLWHA) contain the HIV Negative factor (Nef) protein. However, the role of xEVs and Nef-containing-xEVs(xEV-Nef) in HIV-associated neuropathology is unknown. Here we performed a cross-sectional analysis of the content of xEVs derived from matched serum and CSF samples of PLWHAs diagnosed with either asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). The overall objective was to determine whether the content of the matched xEVs derived plasma or CSF correlated with the neurocognitive impairment (NCI) status. The size and protein content of the xEVs were characterized via dynamic light scattering (DLS) and LC-MS/MS, respectively. xEV size was not significantly different between ANI, MND, or HAD groups. CSF of PLWHAs with NCI contained significantly more xEVs than matched plasma. xEV-Nef CSF concentration was elevated in PLWHAs with NCI and correlated with CD4 T-cell count. Plasma-derived xEV protein profiles from PLWHAs with ANI or MND differed from PLWHAs without NCI. Over-representation analysis using Reactome and KEGG databases show proteins involved in pathways associated with heme scavenging, signaling(MAP kinase and integrin-alpha),Toll-like receptor regulation, clot formation, complement, and cytosolic calcium level were elevated in MND. Pathways upregulated within the ANI group involved high-density lipid (HDL) remodeling, post-translational protein phosphorylation, and platelet activation. Overall, the data shows that xEV protein profiles of ANI and MND differ, suggesting protein profiles of peripheral xEVs, xEV-Nef, and CD4 T-cell count may discern NCI status. Competing Interests: Conflicts of Interest: The authors have no conflict of interest to declare.
Databáze:	MEDLINE
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