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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Antiretroviral Therapy, Highly Active, Cells, Cultured, Cytokines, Dose-Response Relationship, Drug, Extracellular Signal-Regulated MAP Kinases, HIV Infections, HIV-1, HMGB1 Protein, HeLa Cells, Humans, NF-kappa B, Necrosis, Receptor for Advanced Glycation End Products, Receptors, Immunologic, Recombinant Proteins, Transcriptional Activation, Tumor Necrosis Factor-alpha, Virus Activation, Virus Latency, p38 Mitogen-Activated Protein Kinases.
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Does high-mobility group box 1 protein induce HIV-1 expression from persistently infected cells? Context: Necrosis is a frequent condition during AIDS, notably in organs targetted by opportunistic infections. Soluble factors released by necrotic cells are important for signalling cell damage, but little is known concerning their effect on HIV-1 replication. We focused on HMGB1, an abundant component of the chromatin that is released from necrotic cells and can act as a pro-inflammatory mediator. A native form of HMGB1 was obtained from necrotic Hela cells, whereas a purified recombinant HMGB1 was generated in Escherichia coli. ACH-2 and U1 cells were used as models of persistent HIV-1 infection in lymphocytes and monocytes. Reactivation from latency was also investigated ex vivo using peripheral blood mononuclear cells (PBMC) collected from HIV-1-infected patients controlled by HAART. HIV-1 expression was quantified by enzyme-linked immunosorbent assay, real-time reverse transcription-polymerase chain reaction and branched DNA techniques. Flow cytometry and blocking experiments were used to identify the receptor used by HMGB1. Chromatin immunoprecipitation was used to investigate long-terminal repeat activation upon stimulation by HMGB1. HMGB1 increased HIV-1 transcription in chronically infected cells, a process that did not require de-novo protein synthesis. HIV-1 induction relied on HMGB1 interaction with the receptor for advanced glycation end-products. The activation pathway involved p38 and extracellular signal-related kinase as well as nuclear factor kappa B binding to the HIV-1 promoter. Finally, HMGB1 reactivated HIV-1 from latently infected PBMC collected in aviraemic HIV-infected patients.
assistant
This work establishes for the first time a link between necrosis and HIV-1 replication, which involves HMGB1, a soluble mediator released by damaged cells. Final Decision: yes