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Journal of Virology, August 2001, p. 7672-7682, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7672-7682.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Endoplasmic Reticulum and cis-Golgi Localization of Human T-Lymphotropic Virus Type 1 p12^I: Association with Calreticulin and Calnexin

Wei Ding,¹ Björn Albrecht,¹ Rushu Luo,² Weiqing Zhang,^1, James R. L. Stanley,¹ Garret C. Newbound,^1, and Michael D. Lairmore^1,3,4,*

Center for Retrovirus Research and Department of Veterinary Biosciences,¹ Department of Neuroscience, Neurobiotechnology Center,² Comprehensive Cancer Center, The Arthur G. James Cancer Hospital and Solove Research Institute,³ and Department of Molecular Virology, Immunology and Medical Genetics,⁴ The Ohio State University, Columbus, Ohio 43210

Received 12 March 2001/Accepted 18 May 2001

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 p12^I, in establishment of HTLV-1 infection in a rabbit model and for optimal viral infectivity in quiescent primary lymphocytes. These data indicated that p12^I may enhance lymphocyte activation and thereby promote virus infection. To further define the role of p12^I in cell activation, we characterized the subcellular localization of p12^I in transfected 293T cells and HeLa-Tat cells by multiple methods, including immunofluorescence confocal microscopy, electron microscopy, and subcellular fractionation. Herein, we demonstrate that p12^I accumulates in the endoplasmic reticulum (ER) and cis-Golgi apparatus. The location of p12^I 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 p12^I with both calreticulin and calnexin, resident ER proteins which regulate calcium storage. Our results indicate that p12^I directly binds key regulatory proteins involved in calcium-mediated cell signaling and suggest a role of p12^I in the establishment of HTLV-1 infection by activation of host cells.

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^* Corresponding author. Mailing address: Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Rd., Columbus, OH 43210-1092. Phone: (614) 292-4819. Fax: (614) 292-6473. E-mail: Lairmore.1{at}osu.edu.

Present address: Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612-7213.

Present address: Elanco Animal Health, Greenfield, IN 46140.

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Journal of Virology, August 2001, p. 7672-7682, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7672-7682.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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