Journal Article

HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1

Ratner, Lee, Martinez, Michael P., Green, Patrick L., Al-Saleem, Jacob, Dirksen, Wessel P., Shkriabai, Nikoloz, Kvaratskhelia, Mamuka

2019

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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 / Genetic transformation / Glucose / Glucose transport / Glucose Transporter Type 1 - physiology / Health aspects / HEK293 Cells / Heparan sulfate / Hereditary spastic paraplegia / 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