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    HIV heart inflammation is mediated by HIV infected myeloid cells, HIV-tat secretion, and aberrant function of Connexin43-containing channels

    Scientific Reports , Article number:   (2026Cite this article

    We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

    Abstract

    People living with HIV (PLWH) have a 2 times higher risk of HIV-associated cardiovascular disease (HIV-CVD) compared to people without HIV, despite effective anti-retroviral therapy (ART), but the mechanism is unknown. Here, we demonstrated the presence of myeloid cells containing HIV DNA sequences (HIV+) in human ventricular heart tissues from people with HIV in the ART era. HIV+ cells show residual HIV-Tat expression that is associated with upregulation of Connexin43 (Cx43) expression, gap junctional communication, and hemichannel (HC) activity. HIV-Tat binds to the Cx43 promoter, increasing Cx43 mRNA and protein expression. Cx43 enhanced expression by HIV-Tat was localized in the intercalated disk, as well as in the lateral membrane of cardiomyocytes, resulting in Cx43-containing HC openings and release of PGE2 and ATP, as well as facilitating the secretion of inflammatory cytokines. Overall, our data demonstrated that HIV+ cells, even during ART, secrete HIV-Tat, compromising GJ and HC-mediated communication and promoting localized inflammation, which could contribute to arrhythmia.

    Data availability

    All data generated or analyzed during this study are included in this published article and its supplemental information files.

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    Acknowledgements

    We thank the National NeuroAIDS Tissue Consortium (NNTC) for providing all human samples. The NNTC is made possible through funding from the NIMH and NINDS by the following grants: Manhattan HIV Brain Bank (MHBB): U24MH100931; Texas NeuroAIDS Research Center (TNRC): U24MH100930; National Neurological AIDS Bank (NNAB): U24MH100929; California NeuroAIDS Tissue Network (CNTN): U24MH100928; and Data Coordinating Center (DCC): U24MH100925. We want to thank the AIDS NIH repository for providing TZMbL cells, antibodies, and assistance with antibody preparations (Germantown, MD). We thank Dr. Kelly A. Frazer and the University of California San Diego for providing the UCSD143i-87-1/ppiPSC linethrough the iPSCORE resource. We acknowledge the Wellcome Trust Sanger Institute as the source of the WTSIi048-A iPSCline, which was generated under the human induced pluripotent stem cell initiative funded by a grant from the WellcomeTrust and Medical Research Council, supported by the Wellcome Trust (WT098051) and the NIHR/Wellcome Trust ClinicalResearch Facility.

    Funding

    This work was also supported by the James W. McLaughlin Fellowship Funding (to D.A.). CPRIT Recruitment of First-Time Tenure-Track Faculty Award RR190110 (to M.C.W). This work was funded by the National Institute of Mental Health grant, MH128082 and MH134761, the National Institute of Neurological Disorders and Stroke, NS105584, and UTMB internal funding (to E. A. E.).

    Author information

    Authors and Affiliations

    1. Department of Neurobiology, The University of Texas Medical Branch (UTMB), Research Building 17, Fifth Floor, 105 11th Street, Galveston, TX, 77555, USA

      David Ajasin & Eliseo Eugenin

    2. Cardiovascular Research Center, NYU Grossman School of Medicine, New York, NY, USA

      Sophia Arredondo-Anez & Karen Maass

    3. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch (UTMB), Galveston, TX, USA

      Jose A. Gutierrez & Michelle C. Ward

    Contributions

    All authors contributed to the experimental design and writing of the manuscript (D.A., S.A., J.G., M.W., K.M., and E.A.E.). DA performed most of the experiments. S.A. and K.M. performed most of the RNA analyses. J.G. and M.W. performed most of the iPSC experiments. Drs. Mass and Eugenin designed and evaluated the data.

    Corresponding authors

    Correspondence to Karen Maass or Eliseo Eugenin.

    Ethics declarations

    Competing interests

    The authors declare no competing interests.

    IRB approval

    All human tissues in this study were exempt and collected more than 10 years ago; therefore, IRB approval was required from three different research centers. The tissue collection protocols were approved by the Institutional Review Boards of Albert Einstein College of Medicine, Rutgers University, and the University of Texas Medical Branch (Protocol Numbers: Pro20140000794, Pro2012001303, 18–0136, 18–0135, 18–0134 to E.A.E.).

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    Cite this article

    Ajasin, D., Arredondo-Anez, S., Gutierrez, J.A. et al. HIV heart inflammation is mediated by HIV infected myeloid cells, HIV-tat secretion, and aberrant function of Connexin43-containing channels. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43625-2

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    • Received20 July 2025

    • Accepted05 March 2026

    • Published13 March 2026

    • DOIhttps://doi.org/10.1038/s41598-026-43625-2


    This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License

    Source: Nature
    https://www.nature.com/articles/s41598-026-43625-2


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