Enhancement of LFA-1-mediated T cell adhesion by human T lymphotropic virus type 1 p12I1.
Cell-to-cell transmission of retroviruses, such as human T lymphotropic virus type 1 (HTLV-1), is well documented, but the roles of viral regulatory or other nonstructural proteins in the modulation of T cell adhesion are incompletely understood. In this study we tested the role of the HTLV-1 accessory protein, p12(I), on LFA-1-mediated cell adhesion. p12(I) is critical for early HTLV-1 infection by causing the release of calcium from the endoplasmic reticulum to activate NFAT-mediated transcription. We tested the role of this novel viral protein in mediating LFA-1-dependent cell adhesion. Our data indicated that T cells expressing a mutant HTLV-1 provirus that does not produce p12(I) mRNA (ACH.p12(I)) exhibited reduced LFA-1-mediated adhesion compared with wild-type HTLV-1-expressing cells (ACH). Furthermore, the expression of p12(I) in Jurkat T cells using lentiviral vectors enhanced LFA-1-mediated cell adhesion, which was inhibited by the calcium chelator BAPTA-AM, the calcium channel blocker SK&F 96365, and calpeptin, an inhibitor of the calcium-dependent protease calpain. Similar to the intracellular calcium mobilizer, thapsigargin, the expression of p12(I) in Jurkat T cells induced cell surface clustering of LFA-1 without changing the level of integrin expression. Our data are the first to indicate that HTLV-1 p12(I), in addition to enhancing T cell activation, promotes cell-to-cell spread by inducing LFA-1 clustering on T cells via calcium-dependent signaling.
Kim
Seung-Jae
SJ
Center for Retrovirus Research and Department of Veterinary Biosciences, Ohio State University, 1925 Coffey Road, Columbus, OH 43210, USA.
Nair
Amrithraj M
AM
Fernandez
Soledad
S
Mathes
Lawrence
L
Lairmore
Michael D
MD
D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D005786:Gene Expression Regulation; D015368:Human T-lymphotropic virus 1 / Q000145:classification / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D005810:Multigene Family / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D016169:Lymphocyte Function-Associated Antigen-1; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C084305:p12I protein, Human T-lymphotropic virus 1; D018799:Intercellular Adhesion Molecule-1; D002118:Calcium