Phospholipase D1 Couples CD4 T Cell Activation to c-Myc-Dependent Deoxyribonucleotide Pool Expansion and HIV-1 Replication

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Replication of all human viruses depends on building blocks derived from the metabolic pathways of the infected host cell. The production of progeny virions requires synthesis of viral nucleic acids from deoxyribonucleotide triphosphates (dNTPs). HIV-1 infection in resting T cells is limited, at least in part, because the levels of critical nucleotides are low. However, stimulation of T cells turns on their metabolic machinery to increase c-Myc expression and subsequent synthesis of these key components of RNA and DNA, which augments HIV-1 replication. We have identified PLD1 as a key molecular switch that couples stimulatory T cell signals to c-Myc-dependent nucleotide biosynthesis. We also found that a small molecule that inhibits PLD1 suppresses HIV-1 replication by limiting c-Myc-dependent effects of T cell activation that support efficient HIV reverse transcription. Our study provides insight into a novel way of targeting T cell activation-induced processes such as nucleotide biosynthesis that has potential to augment current therapeutics for HIV-1.

Vyšlo v časopise: Phospholipase D1 Couples CD4 T Cell Activation to c-Myc-Dependent Deoxyribonucleotide Pool Expansion and HIV-1 Replication. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004864
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004864

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