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• W2894367457 abstract "Abstract Persistence of latent HIV-1 in macrophages (MACs) and T-helper lymphocytes (THLs) remain a major therapeutic challenge. Currently available latency reversing agents (LRAs) are not very effective in vivo . Therefore, understanding of physiologic mechanisms that dictate HIV-1 latency/reactivation in reservoirs is clearly needed. Mesenchymal stromal/stem cells (MSCs) regulate the function of immune cells; however, their role in regulating virus production from latently-infected MACs & THLs is not known. We documented that exposure to MSCs or their conditioned media (MSC-CM) rapidly increased HIV-1 p24 production from the latently-infected U1 (MAC) & ACH2 (THL) cell lines. Exposure to MSCs also increased HIV-1 long terminal repeat (LTR) directed gene expression in the MAC and THL reporter lines, U937-VRX and J-Lat (9.2), respectively. MSCs exposed to CM from U1 cells (U1-CM) showed enhanced migratory ability towards latently-infected cells and retained their latency-reactivation potential. Molecular studies showed that MSC-mediated latency-reactivation was dependent upon both the phosphatidyl inositol-3-kinase (PI3K) and nuclear factor-κB (NFκB) signaling pathways. The pre-clinically tested inhibitors of PI3K (PX-866) and NFκB (CDDO-Me) suppressed MSC-mediated HIV-1 reactivation. Furthermore, coexposure to MSC-CM enhanced the latency-reactivation efficacy of the approved LRAs, vorinostat and panobinostat. Our findings on MSC-mediated latency-reactivation may provide novel strategies against persistent HIV-1 reservoirs." @default.
• W2894367457 created "2018-10-05" @default.
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• W2894367457 date "2018-10-02" @default.
• W2894367457 modified "2023-10-12" @default.
• W2894367457 title "Mesenchymal stem cells are attracted to latent HIV-1-infected cells and enable virus reactivation via a non-canonical PI3K-NFκB signaling pathway" @default.
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• W2894367457 doi "https://doi.org/10.1038/s41598-018-32657-y" @default.
• W2894367457 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6168583" @default.
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