Journal article
Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein
The Journal of biological chemistry, v 289(32), pp 22284-22305
08 Aug 2014
PMID: 24939845
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. The HTLV-1 transactivator protein Tax controls many critical cellular pathways, including host cell DNA damage response mechanisms, cell cycle progression, and apoptosis. Extracellular vesicles called exosomes play critical roles during pathogenic viral infections as delivery vehicles for host and viral components, including proteins, mRNA, and microRNA. We hypothesized that exosomes derived from HTLV-1-infected cells contain unique host and viral proteins that may contribute to HTLV-1-induced pathogenesis. We found exosomes derived from infected cells to contain Tax protein and proinflammatory mediators as well as viral mRNA transcripts, including Tax, HBZ, and Env. Furthermore, we observed that exosomes released from HTLV-1-infected Tax-expressing cells contributed to enhanced survival of exosome-recipient cells when treated with Fas antibody. This survival was cFLIP-dependent, with Tax showing induction of NF-κB in exosome-recipient cells. Finally, IL-2-dependent CTLL-2 cells that received Tax-containing exosomes were protected from apoptosis through activation of AKT. Similar experiments with primary cultures showed protection and survival of peripheral blood mononuclear cells even in the absence of phytohemagglutinin/IL-2. Surviving cells contained more phosphorylated Rb, consistent with the role of Tax in regulation of the cell cycle. Collectively, these results suggest that exosomes may play an important role in extracellular delivery of functional HTLV-1 proteins and mRNA to recipient cells.
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Details
- Title
- Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein
- Creators
- Elizabeth Jaworski - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110Aarthi Narayanan - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110Rachel Van Duyne - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110, the Department of Microbiology, Immunology, and Tropical Medicine andShabana Shabbeer-Meyering - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110Sergey Iordanskiy - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110, the Department of Microbiology, Immunology, and Tropical Medicine andMohammed Saifuddin - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110Ravi Das - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110Philippe V Afonso - the Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Département de Virologie, Institut Pasteur, F-75015 Paris, France, CNRS, UMR3569, F-75015 Paris, France, andGavin C Sampey - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110Myung Chung - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110Anastas Popratiloff - the Department of Chemistry, George Washington University, Washington, D. C. 20037Bindesh Shrestha - Center for Microscopy and Image Analysis, George Washington University Medical Center, Washington, D. C. 20037Mohit Sehgal - the Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, Pennsylvania 18902Pooja Jain - the Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, Pennsylvania 18902Akos Vertes - Center for Microscopy and Image Analysis, George Washington University Medical Center, Washington, D. C. 20037Renaud Mahieux - the Equipe Oncogenèse Rétrovirale, Equipe labelisée "Ligue Nationale Contre le Cancer," International Center for Research in Infectiology, INSERM U1111-CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon 69364 Cedex 07, FranceFatah Kashanchi - From the School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110, fkashanc@gmu.edu
- Publication Details
- The Journal of biological chemistry, v 289(32), pp 22284-22305
- Publisher
- ASBMB Publications / Elsevier; United States
- Grant note
- R01 CA054559 / NCI NIH HHS AI078859 / NIAID NIH HHS R01 AI077414 / NIAID NIH HHS AI074410 / NIAID NIH HHS R01 AI043894 / NIAID NIH HHS R21 AI074410 / NIAID NIH HHS AI043894 / NIAID NIH HHS R21 AI078859 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000340593500041
- Scopus ID
- 2-s2.0-84905833500
- Other Identifier
- 991014877999904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology