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Volume 27
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10.3390/ijms27020966
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

SHIV.D Infection Alters Production and Protein Composition of Myeloid-Derived Extracellular Vesicles

by
Rachel M. Podgorski
1,
Amir Yarmahmoodi
2,
Stephen Baak
1,
Rebecca Warfield
1,
Jake A. Robinson
3,
Jennifer Roof
4,
Maurizio Caocci
5,
Hossein Fazelinia
4,
Lynn A. Spruce
4,
Katharine J. Bar
3 and
Tricia H. Burdo
5,*
1
Center for NeuroVirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
2
Flow Cytometry Core Facility, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
3
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4
Proteomics Core Facility, Children’s Hospital of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19104, USA
5
Department of Medicine, Rutgers Institute of Translational Medicine and Science, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(2), 966; https://doi.org/10.3390/ijms27020966 (registering DOI)
Submission received: 17 December 2025 / Revised: 13 January 2026 / Accepted: 15 January 2026 / Published: 18 January 2026
(This article belongs to the Section Molecular Nanoscience)
Versions Notes

Abstract

Although neurological disease is common in people with human immunodeficiency virus (HIV) (PWH), the contributing factors and underlying inflammatory mechanisms remain challenging to identify. Extracellular vesicles (EVs) constitute a relatively uncharacterized modality of intercellular communication and bioactive cargo transport in the setting of viral infection and pathogenesis. EVs carry inflammatory mediators to areas of the periphery during antiretroviral therapy (ART) suppression but are understudied in the brain. Using a biologically relevant simian–human immunodeficiency chimeric virus with a clade D HIV envelope (SHIV.D)-infected rhesus macaque (RM) model of HIV persistence in the central nervous system (CNS), we investigate circulating EV populations and the protein cargo of myeloid-derived EVs during SHIV infection. Using EV flow cytometry to quantify specific EV subpopulations, we found a significant increase in TMEM119+ microglial EVs and CD171+ neuronal EVs in RM plasma during viremia and ART suppression. Using primary RM monocyte-derived macrophages (MDMs), we determined that MDMs increased EV production after SHIV infection. Whole proteomic analysis of these EVs demonstrated that myeloid EVs isolated from SHIV.D-infected MDMs carried significantly increased levels of neuropathogenic and inflammatory proteins. Altogether, these studies improve our understanding of the contribution of myeloid EVs to neurological disease during SHIV/HIV infection.
Keywords: extracellular vesicles; neuroinflammation; SHIV; HIV; viral persistence extracellular vesicles; neuroinflammation; SHIV; HIV; viral persistence

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MDPI and ACS Style

Podgorski, R.M.; Yarmahmoodi, A.; Baak, S.; Warfield, R.; Robinson, J.A.; Roof, J.; Caocci, M.; Fazelinia, H.; Spruce, L.A.; Bar, K.J.; et al. SHIV.D Infection Alters Production and Protein Composition of Myeloid-Derived Extracellular Vesicles. Int. J. Mol. Sci. 2026, 27, 966. https://doi.org/10.3390/ijms27020966

AMA Style

Podgorski RM, Yarmahmoodi A, Baak S, Warfield R, Robinson JA, Roof J, Caocci M, Fazelinia H, Spruce LA, Bar KJ, et al. SHIV.D Infection Alters Production and Protein Composition of Myeloid-Derived Extracellular Vesicles. International Journal of Molecular Sciences. 2026; 27(2):966. https://doi.org/10.3390/ijms27020966

Chicago/Turabian Style

Podgorski, Rachel M., Amir Yarmahmoodi, Stephen Baak, Rebecca Warfield, Jake A. Robinson, Jennifer Roof, Maurizio Caocci, Hossein Fazelinia, Lynn A. Spruce, Katharine J. Bar, and et al. 2026. "SHIV.D Infection Alters Production and Protein Composition of Myeloid-Derived Extracellular Vesicles" International Journal of Molecular Sciences 27, no. 2: 966. https://doi.org/10.3390/ijms27020966

APA Style

Podgorski, R. M., Yarmahmoodi, A., Baak, S., Warfield, R., Robinson, J. A., Roof, J., Caocci, M., Fazelinia, H., Spruce, L. A., Bar, K. J., & Burdo, T. H. (2026). SHIV.D Infection Alters Production and Protein Composition of Myeloid-Derived Extracellular Vesicles. International Journal of Molecular Sciences, 27(2), 966. https://doi.org/10.3390/ijms27020966

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