Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis

• Published in: Viruses Vol. 15; no. 3; p. 794
• Main Authors: Chandra, Partha K., Braun, Stephen E., Maity, Sudipa, Castorena-Gonzalez, Jorge A., Kim, Hogyoung, Shaffer, Jeffrey G., Cikic, Sinisa, Rutkai, Ibolya, Fan, Jia, Guidry, Jessie J., Worthylake, David K., Li, Chenzhong, Abdel-Mageed, Asim B., Busija, David W.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.03.2023; MDPI
• Subjects: Actin; Adenosine Triphosphate; Alzheimer's disease; Animal welfare; Animals; antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Autophagy; biogenesis; Blood proteins; Blood-brain barrier; brain; CD31 antigen; cell adhesion; Cell adhesion molecules; Cell organelles; Central nervous system; Central nervous system diseases; Chromatography; circulating plasma exosomes; Cognition; Cognition disorders; Complications and side effects; Cytoskeleton; Cytotoxicity; Development and progression; Disease Models, Animal; Endocytosis; Endothelial Cells; Etiology; Exocytosis; Exosomes; Health aspects; HIV; HIV infection; HIV infections; HIV Infections - complications; HIV-1; Human immunodeficiency virus; Humans; Immune system; Inflammation; Laboratory animals; Lymphocytes T; Macaca mulatta; Manufacturers; Mass spectrometry; Membrane permeability; microfilaments; Microvasculature; Mitochondria; Neuropathogenesis; Oxidative stress; Parkinson's disease; particle size; Pathology; Patients; permeability; Plasma; Protein structure; Proteins; proteomic analysis; Proteomics; rhesus macaque; Risk factors; Scientific imaging; SHIV; Simian Acquired Immunodeficiency Syndrome - complications; Simian Immunodeficiency Virus; therapeutics; Viral Load; United States; United States > US; HIV-1; rhesus macaque; SHIV; neuropathogenesis; circulating plasma exosomes; proteomic analysis
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15030794

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.