Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis
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 th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/3/794 |
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| author | Partha K. Chandra Stephen E. Braun Sudipa Maity Jorge A. Castorena-Gonzalez Hogyoung Kim Jeffrey G. Shaffer Sinisa Cikic Ibolya Rutkai Jia Fan Jessie J. Guidry David K. Worthylake Chenzhong Li Asim B. Abdel-Mageed David W. Busija |
| author_facet | Partha K. Chandra Stephen E. Braun Sudipa Maity Jorge A. Castorena-Gonzalez Hogyoung Kim Jeffrey G. Shaffer Sinisa Cikic Ibolya Rutkai Jia Fan Jessie J. Guidry David K. Worthylake Chenzhong Li Asim B. Abdel-Mageed David W. Busija |
| author_sort | Partha K. Chandra |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:45:30Z |
| format | Article |
| id | doaj.art-229353644e9f4202a6485649497b10fd |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T05:45:30Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-229353644e9f4202a6485649497b10fd2023-11-17T14:24:27ZengMDPI AGViruses1999-49152023-03-0115379410.3390/v15030794Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to NeuropathogenesisPartha K. Chandra0Stephen E. Braun1Sudipa Maity2Jorge A. Castorena-Gonzalez3Hogyoung Kim4Jeffrey G. Shaffer5Sinisa Cikic6Ibolya Rutkai7Jia Fan8Jessie J. Guidry9David K. Worthylake10Chenzhong Li11Asim B. Abdel-Mageed12David W. Busija13Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Biostatistics and Data Science, Tulane University, New Orleans, LA 70112, USADepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USAProteomics Core Facility, Louisiana State University, New Orleans, LA 70112, USAProteomics Core Facility, Louisiana State University, New Orleans, LA 70112, USADepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USADespite 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.https://www.mdpi.com/1999-4915/15/3/794HIV-1SHIVcirculating plasma exosomesneuropathogenesisrhesus macaqueproteomic analysis |
| spellingShingle | Partha K. Chandra Stephen E. Braun Sudipa Maity Jorge A. Castorena-Gonzalez Hogyoung Kim Jeffrey G. Shaffer Sinisa Cikic Ibolya Rutkai Jia Fan Jessie J. Guidry David K. Worthylake Chenzhong Li Asim B. Abdel-Mageed David W. Busija Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis Viruses HIV-1 SHIV circulating plasma exosomes neuropathogenesis rhesus macaque proteomic analysis |
| title | Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis |
| title_full | Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis |
| title_fullStr | Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis |
| title_full_unstemmed | Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis |
| title_short | Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis |
| title_sort | circulating plasma exosomal proteins of either shiv infected rhesus macaque or hiv infected patient indicates a link to neuropathogenesis |
| topic | HIV-1 SHIV circulating plasma exosomes neuropathogenesis rhesus macaque proteomic analysis |
| url | https://www.mdpi.com/1999-4915/15/3/794 |
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