Enhancement of LFA-1-mediated T cell adhesion by human T lymphotropic virus type 1 p12I1

Seung Jae Kim, Amrithraj M. Nair, Soledad Fernandez, Lawrence Mathes, Michael Dale Lairmore

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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, p12I, 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 p12I mRNA (ACH.p12I) exhibited reduced LFA-1-mediated adhesion compared with wild-type HTLV-1-expressing cells (ACH). Furthermore, the expression of p12I 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 p12I, in addition to enhancing T cell activation, promotes cell-to-cell spread by inducing LFA-1 clustering on T cells via calcium-dependent signaling.

Original languageEnglish (US)
Pages (from-to)5463-5470
Number of pages8
JournalJournal of Immunology
Volume176
Issue number9
StatePublished - May 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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