Exosomal Tat protein activates latent HIV-1 in primary, resting CD4+ T lymphocytes
| Autor: | Bharat Ramratnam, Stacey Chapman, Huafei Lu, Xiaoli Tang, Peter J. Quesenberry, Mark S. Dooner |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Male Anti-HIV Agents Recombinant Fusion Proteins Primary Cell Culture HIV Infections Biology Hiv 1 tat Exosomes Protein Engineering Transfection Virus Replication Proto-Oncogene Proteins c-myc 03 medical and health sciences Transactivation Latent Virus In vivo Transcription (biology) Antiretroviral Therapy Highly Active Potency Humans Cloning Molecular Cell Engineering Aged Drug Carriers General Medicine Provirus Middle Aged Virology Microvesicles Virus Latency 030104 developmental biology HEK293 Cells HIV-1 Female tat Gene Products Human Immunodeficiency Virus Research Article |
| Popis: | Replication competent HIV-1 persists in a subpopulation of CD4+ T lymphocytes despite prolonged antiretroviral treatment. This residual reservoir of infected cells harbors transcriptionally silent provirus capable of reigniting productive infection upon discontinuation of antiretroviral therapy. Certain classes of drugs can activate latent virus but not at levels that lead to reductions in HIV-1 reservoir size in vivo. Here, we show the utility of CD4+ receptor targeting exosomes as an HIV-1 latency reversal agent (LRA). We engineered human cellular exosomes to express HIV-1 Tat, a protein that is a potent transactivator of viral transcription. Preparations of exosomal Tat-activated HIV-1 in primary, resting CD4+ T lymphocytes isolated from antiretroviral-treated individuals with prolonged periods of viral suppression and led to the production of replication competent HIV-1. Furthermore, exosomal Tat increased the potency of selected LRA by over 30-fold in terms of HIV-1 mRNA expression, thereby establishing it as a potentially new class of biologic product with possible combinatorial utility in targeting latent HIV-1. |
| Databáze: | OpenAIRE |
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