Adenosine Deaminase--metabolism; CD4-Positive T-Lymphocytes--virolog; HIV Infections--virology; HIV-1--pathogenicity; RNA-Binding Proteins--metabolism; Virus Replication
Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of protein translation. Furthermore, viral protein synthesis block is accompanied by an activation of interferon-stimulated genes. RNA silencing of ADAR1 in Jurkat cells also inhibited HIV-1 protein synthesis. Our data support that HIV-1 requires ADAR1 for efficient replication in human CD4+T cells.
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Cuadrado, E., Booiman, T., Van Hamme, J.L., Jansen, M.H., Van Dort, K.A.,...Kuijpers, T.W. (2015). ADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells. PLoS ONE, 10(12), e0143613. doi: 10.1371/journal.pone.0143613