دورية أكاديمية
Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells
العنوان: | Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells |
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المؤلفون: | Melanie Dimapasoc, Jose Moran, Steve Cole, Alok Ranjan, Rami Hourani, Jocelyn Kim, Paul Wender, Matthew Marsden, Jerome Zack |
المصدر: | Pathogens and Immunity, Vol 9, Iss 1 (2024) |
بيانات النشر: | Case Western Reserve University, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Pathology LCC:Immunologic diseases. Allergy |
مصطلحات موضوعية: | Killer Cells, Natural, Protein Kinase C, HIV-1, Virus Latency, Immunity, Acquired Immunodeficiency Syndrome, Pathology, RB1-214, Immunologic diseases. Allergy, RC581-607 |
الوصف: | Background: Latency reversing agents (LRAs) such as protein kinase C (PKC) modulators can reduce rebound-competent HIV reservoirs in small animal models. Furthermore, administration of natural killer (NK) cells following LRA treatment improves this reservoir reduction. It is currently unknown why the combination of a PKC modulator and NK cells is so potent and whether exposure to PKC modulators may augment NK cell function in some way. Methods: Primary human NK cells were treated with PKC modulators (bryostatin-1, prostratin, or the designed, synthetic bryostatin-1 analog SUW133), and evaluated by examining expression of activation markers by flow cytometry, analyzing transcriptomic profiles by RNA sequencing, measuring cytotoxicity by co-culturing with K562 cells, assessing cytokine production by Luminex assay, and examining the ability of cytokines and secreted factors to independently reverse HIV latency by co-culturing with Jurkat-Latency (J-Lat) cells. Results: PKC modulators increased expression of proteins involved in NK cell activation. Transcriptomic profiles from PKC-treated NK cells displayed signatures of cellular activation and enrichment of genes associated with the NFκB pathway. NK cell cytotoxicity was unaffected by prostratin but significantly decreased by bryostatin-1 and SUW133. Cytokines from PKC-stimulated NK cells did not induce latency reversal in J-Lat cell lines. Conclusions: Although PKC modulators have some significant effects on NK cells, their contribution in “kick and kill” strategies is likely due to upregulating HIV expression in CD4+ T cells, not directly enhancing the effector functions of NK cells. This suggests that PKC modulators are primarily augmenting the “kick” rather than the “kill” arm of this HIV cure approach. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2469-2964 |
Relation: | https://www.paijournal.com/index.php/paijournal/article/view/673; https://doaj.org/toc/2469-2964 |
DOI: | 10.20411/pai.v9i1.673 |
URL الوصول: | https://doaj.org/article/b28795ccc8294c6cb9c59f2b4d84955c |
رقم الأكسشن: | edsdoj.b28795ccc8294c6cb9c59f2b4d84955c |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 24692964 |
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DOI: | 10.20411/pai.v9i1.673 |