Endoplasmic Reticulum andcis-Golgi Localization of Human T-Lymphotropic Virus Type 1 p12I: Association with Calreticulin and Calnexin
Open Access
- 15 August 2001
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 75 (16) , 7672-7682
- https://doi.org/10.1128/jvi.75.16.7672-7682.2001
Abstract
Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus encoding regulatory and accessory genes in four open reading frames (ORF I to IV) of the pX region. We have demonstrated an important role of pX ORF I expression, which encodes p12I, in establishment of HTLV-1 infection in a rabbit model and for optimal viral infectivity in quiescent primary lymphocytes. These data indicated that p12I may enhance lymphocyte activation and thereby promote virus infection. To further define the role of p12I in cell activation, we characterized the subcellular localization of p12I in transfected 293T cells and HeLa-Tat cells by multiple methods, including immunofluorescence confocal microscopy, electron microscopy, and subcellular fractionation. Herein, we demonstrate that p12I accumulates in the endoplasmic reticulum (ER) and cis-Golgi apparatus. The location of p12I was unchanged following treatments with both cycloheximide (blocking de novo protein synthesis) and brefeldin A (disrupting ER-to-Golgi protein transport), indicating that the protein is retained in the ER and cis-Golgi. Moreover, using coimmunoprecipitation assays, we identify the direct binding of p12I with both calreticulin and calnexin, resident ER proteins which regulate calcium storage. Our results indicate that p12I directly binds key regulatory proteins involved in calcium-mediated cell signaling and suggest a role of p12Iin the establishment of HTLV-1 infection by activation of host cells.Keywords
This publication has 76 references indexed in Scilit:
- The MHC Class I Heavy Chain Is a Common Target of the Small Proteins Encoded by the 3′ End of HTLV Type 1 and HTLV Type 2AIDS Research and Human Retroviruses, 2000
- Gelsolin Inhibits Apoptosis by Blocking Mitochondrial Membrane Potential Loss and Cytochrome c ReleasePublished by Elsevier ,2000
- Substitution of the Two Carboxyl-terminal Serines by Alanine Causes Retention of MAL, a Component of the Apical Sorting Machinery, in the Endoplasmic ReticulumBiochemical and Biophysical Research Communications, 1999
- Molecular Cloning, Characterization, and Dynamics of Rat Formiminotransferase Cyclodeaminase, a Golgi-associated 58-kDa ProteinPublished by Elsevier ,1998
- Presenilin 1 Regulates the Processing of β-Amyloid Precursor Protein C-Terminal Fragments and the Generation of Amyloid β-Protein in Endoplasmic Reticulum and GolgiBiochemistry, 1998
- Human T-cell leukemia viruses: epidemiology, biology, and pathogenesisBlood Reviews, 1997
- HUMAN T CELL LEUKEMIA VIRUS TYPE I (HTLV-I) AND HUMAN DISEASESAnnual Review of Immunology, 1997
- Mapping of the intermolecular association of the human T cell leukaemia/lymphotropic virus type I p12I and the vacuolar H+-ATPase 16 kDa subunit proteinJournal of General Virology, 1995
- Small GTP-binding proteins and their role in transportCurrent Opinion in Cell Biology, 1991
- Trans -Acting Transcriptional Activation of the Long Terminal Repeat of Human T Lymphotropic Viruses in Infected CellsScience, 1984