Details
- Autor(en) / Beteiligte
- Titel
- HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1
- Ist Teil von
- PloS one, 2019-03, Vol.14 (3), p.e0214059-e0214059
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- An estimated 10-20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replication, as it drives transcription of viral gene products, and has also been demonstrated to play a key role in the pathogenesis of the virus. Several studies have identified a PDZ binding motif (PBM) at the carboxyl terminus of Tax-1 and demonstrated the importance of this domain for HTLV-1 induced cellular transformation. Using a mass spectrometry-based proteomics approach we identified sorting nexin 27 (SNX27) as a novel interacting partner of Tax-1. Further, we demonstrated that their interaction is mediated by the Tax-1 PBM and SNX27 PDZ domains. SNX27 has been shown to promote the plasma membrane localization of glucose transport 1 (GLUT1), one of the receptor molecules of the HTLV-1 virus, and the receptor molecule required for HTLV-1 fusion and entry. We postulated that Tax-1 alters GLUT1 localization via its interaction with SNX27. We demonstrate that over expression of Tax-1 in cells causes a reduction of GLUT1 on the plasma membrane. Furthermore, we show that knockdown of SNX27 results in increased virion release and decreased HTLV-1 infectivity. Collectively, we demonstrate the first known mechanism by which HTLV-1 regulates a receptor molecule post-infection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0214059Titel-ID: cdi_plos_journals_2195912980
- Format
- –
- Schlagworte
- Adult T cell leukemia, Amino Acid Sequence, Analysis, Backup software, Biology and life sciences, Cell membranes, Domains, gag Gene Products, Human Immunodeficiency Virus - physiology, Gene Knockdown Techniques, Gene Products, tax - chemistry, Gene Products, tax - genetics, Gene Products, tax - physiology, Genes, Genetic aspects, Glucose, Glucose transport, Glucose Transporter Type 1 - physiology, Health aspects, HEK293 Cells, Heparan sulfate, HIV infection, HIV infections, Host Microbial Interactions - genetics, Host Microbial Interactions - physiology, HTLV-I Infections - genetics, HTLV-I Infections - physiopathology, HTLV-I Infections - virology, Human T-lymphotropic virus 1 - genetics, Human T-lymphotropic virus 1 - pathogenicity, Human T-lymphotropic virus 1 - physiology, Humans, Infection, Infections, Infectious diseases, Infectivity, Leukemia, Life cycles, Localization, Lymphocytes, Lymphocytes T, Mass spectrometry, Mass spectroscopy, Medicine and Health Sciences, Models, Biological, Myopathy, Nexin, Novels, Pathogenesis, PDZ Domains, Protein Interaction Domains and Motifs, Proteins, Proteomics, Receptors, Virus - physiology, Research and Analysis Methods, Sorting Nexins - chemistry, Sorting Nexins - genetics, Sorting Nexins - physiology, Spastic paraparesis, Spectroscopy, T cells, Taxation, Transcription, Transcription (Genetics), Transformation, Virions, Virology, Virulence - genetics, Virulence - physiology, Virus replication, Viruses