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PMID: 11462039 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic virus type 1 p12(I): association with calreticulin and calnexin.

Journal of virology ·Vol. 75 ·No. 16 ·2001-08-00 ·Pages 7672-82

Ding W, Albrecht B, Luo R, Zhang W, Stanley JR, Newbound GC, Lairmore MD

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 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.

MeSH Terms
Biological Transport Calcium-Binding Proteins/physiology Calnexin Calreticulin Cell Line Endoplasmic Reticulum/virology Golgi Apparatus/virology HTLV-I Infections/metabolism,pathology,virology Human T-lymphotropic virus 1/physiology Humans Ribonucleoproteins/physiology Virus Replication
Chemicals
Calcium-Binding Proteins Calreticulin Ribonucleoproteins Calnexin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ding W
Department of Veterinary Biosciences, The Arthur G. James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA.
Albrecht B
Luo R
Zhang W
Stanley J R
Newbound G C
Lairmore M D
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.16.7672-7682.2001
Published
2001-08-00
Pages
7672-82
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC115002
Subset
IM
Grants
NCRR NIH HHS · R01 RR014324 · United States
NCI NIH HHS · CA-70529 · United States
NIAID NIH HHS · K02 AI01474 · United States
NCRR NIH HHS · RR-14324 · United States
External Links
PubMed source DOI: 10.1128/JVI.75.16.7672-7682.2001 PMC Full Text View journal details
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