1. Alpha Interferon Restricts Human T-Lymphotropic Virus Type 1 and 2 De Novo Infection through PKR Activation
- Author
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Renaud Mahieux, Nga Ling Ko, Chloé Journo, Sandrine Alais, Sébastien Chevalier, Hélène Dutartre, Lee Ratner, Anne Cachat, Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Small interfering RNA ,[SDV]Life Sciences [q-bio] ,viruses ,medicine.medical_treatment ,Cellular Response to Infection ,MESH: Recombinant Proteins ,eIF-2 Kinase ,0302 clinical medicine ,immune system diseases ,Interferon ,Human T-lymphotropic virus 1 ,0303 health sciences ,biology ,Human T-lymphotropic virus 2 ,virus diseases ,Recombinant Proteins ,3. Good health ,Cytokine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,MESH: Interferon-alpha ,MESH: HTLV-II Infections ,medicine.drug ,MESH: Enzyme Activation ,T cell ,Immunology ,Alpha interferon ,Interferon alpha-2 ,Microbiology ,Cell Line ,MESH: eIF-2 Kinase ,03 medical and health sciences ,MESH: HTLV-I Infections ,Virology ,medicine ,Humans ,030304 developmental biology ,MESH: Human T-lymphotropic virus 1 ,MESH: Humans ,MESH: Human T-lymphotropic virus 2 ,MESH: Host-Pathogen Interactions ,Interferon-alpha ,biology.organism_classification ,HTLV-I Infections ,Protein kinase R ,MESH: Cell Line ,Enzyme Activation ,Cell culture ,Insect Science ,HTLV-II Infections - Abstract
Type I interferon (IFN-I) inhibits the replication of different viruses. However, the effect of IFN-I on the human T-lymphotropic virus type 1 (HTLV-1) viral cycle is controversial. Here, we investigated the consequences of IFN-α addition for different steps of HTLV-1 and HTLV-2 infection. We first show that alpha interferon (IFN-α) efficiently impairs HTLV-1 and HTLV-2 de novo infection in a T cell line and in primary lymphocytes. Using pseudotyped viruses expressing HTLV-1 envelope, we then show that cell-free infection is insensitive to IFN-α, demonstrating that the cytokine does not affect the early stages of the viral cycle. In contrast, intracellular levels of Gag, Env, or Tax protein are affected by IFN-α treatment in T cells, primary lymphocytes, or 293T cells transfected with HTLV-1 or HTLV-2 molecular clones, demonstrating that IFN-α acts during the late stages of infection. We show that IFN-α does not affect Tax-mediated transcription and acts at a posttranscriptional level. Using either small interfering RNA (siRNA) directed against PKR or a PKR inhibitor, we demonstrate that PKR, whose expression is induced by interferon, plays a major role in IFN-α-induced HTLV-1/2 inhibition. These results indicate that IFN-α has a strong repressive effect on the HTLV-1 and HTLV-2 viral cycle during de novo infection of cells that are natural targets of the viruses.
- Published
- 2013