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Chronic brain damage in HIV-infected individuals under antiretroviral therapy is associated with viral reservoirs, sulfatide release, and compromised cell-to-cell communication

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Abstract

HIV infection has become a chronic and manageable disease due to the effective use of antiretroviral therapies (ART); however, several chronic aging-related comorbidities, including cognitive impairment, remain a major public health issue. However, these mechanisms are unknown. Here, we identified that glial and myeloid viral reservoirs are associated with local myelin damage and the release of several myelin components, including the lipid sulfatide. Soluble sulfatide compromised gap junctional communication and calcium wave coordination, essential for proper cognition. We propose that soluble sulfatide could be a potential biomarker and contributor to white matter compromise observed in HIV-infected individuals even in the current ART era.

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Funding

This work was funded by The National Institute of Mental Health grant, MH128082, the National Institute of Neurological Disorders and Stroke, NS105584, from the UTMB Sealy Institute for Vaccine Sciences and the UTMB Institute for Human Infection &Immunity (to EAE).

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  1. Brendan Prideaux and Eliseo A. Eugenin contributed equally to this work.

Authors and Affiliations

  1. Department of Neurobiology, The University of Texas Medical Branch (UTMB), Research Building 17, Fifth Floor, 11Th Street, Galveston, TX, 77555, USA

    Daniela D’Amico, Brendan Prideaux & Eliseo A. Eugenin

  2. Department of Biomedicine, Neuroscience, and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy

    Daniela D’Amico, Rosario Barone & Valentina Di Felice

  3. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

    Beau Ances

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  1. Daniela D’Amico
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  4. Beau Ances
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Contributions

Study concepts and design were undertaken by BP, and EAE Data acquisition and analysis were undertaken for DD BP and EAE Manuscript suggestions and writing was provided for all authors.

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Correspondence to Brendan Prideaux or Eliseo A. Eugenin.

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D’Amico, D., Barone, R., Di Felice, V. et al. Chronic brain damage in HIV-infected individuals under antiretroviral therapy is associated with viral reservoirs, sulfatide release, and compromised cell-to-cell communication. Cell. Mol. Life Sci. 80, 116 (2023). https://doi.org/10.1007/s00018-023-04757-0

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