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

Authors

Partha K. Chandra, Tulane University School of Medicine, New Orleans, LA
Stephen E. Braun, Tulane University School of Medicine, New Orleans, LA
Sudipa Maity, Tulane National Primate Research Center, Covington, LA
Jorge A. Castorena-Gonzalez, Tulane University School of Medicine, New Orleans, LA
Hogyoung Kim, Tulane University School of Medicine, New Orleans, LA
Jeffrey G. Shaffer, Tulane University, New Orleans, LA
Sinisa Cikic, Tulane University School of Medicine, New Orleans, LA
Ibolya Rutkai, Tulane University School of Medicine, New Orleans, LA
Jia Fan, Tulane University School of Medicine, New Orleans, LA
Jessie J. Guidry, LSU Health Sciences Center - New Orleans
David K. Worthylake, LSU Health Sciences Center - New Orleans
Chenzhong Li, Tulane University School of Medicine, New Orleans, LA
Asim B. Abdel-Mageed, Tulane University School of Medicine, New Orleans, LA
David W. Busija, Tulane University School of Medicine, New Orleans, LA

Document Type

Article

Publication Date

3-21-2023

Publication Title

Viruses

Abstract

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.

PubMed ID

36992502

Volume

15

Issue

3

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

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.; and Busija, David W., "Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis" (2023). School of Medicine Faculty Publications. 2054.
https://digitalscholar.lsuhsc.edu/som_facpubs/2054