Human T-cell lymphotropic virus type 1 p12I enhances interleukin-2 production during T-cell activation

Wei Ding, Seung Jae Kim, Amrithraj M. Nair, Bindhu Michael, Kathleen Boris-Lawrie, Adam Tripp, Gerold Feuer, Michael D. Lairmore

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and a variety of lymphoproliferative disorders. The early virus-cell interactions that determine a productive infection remain unclear. However, it is well recognized that T-cell activation is required for effective retroviral integration into the host cell genome and subsequent viral replication. The HTLV-1 pX open reading frame I encoding protein, p12 I, is critical for the virus to establish persistent infection in vivo and for infection in quiescent primary lymphocytes in vitro, p12 I localizes in the endoplasmic reticulum (ER) and cis-Golgi apparatus, increases intracellular calcium and activates nuclear factor of activated T cells (NFAT)-mediated transcription. To clarify the function of p12I, we tested the production of IL-2 from Jurkat T celis cells and peripheral blood mononuclear cells (PBMC) expressing p12I. Lentiviral vector expressed p12I in Jurkat T cells enhanced interleukin-2 (IL-2) production in a calcium pathway-dependent manner during T-cell receptor (TCR) stimulation. Expression of p12I also induced higher NFAT-mediated reporter gene activities during TCR stimulation in Jurkat T cells. In contrast, p12 expression in PBMC elicited increased IL-2 production in the presence of phorbal ester stimulation, but not during TCR stimulation. Finally, the requirement of ER localization for p12I-mediated NFAT activation was demonstrated and two positive regions and two negative regions in p12I were identified for the activation of this transcription factor by using p12I truncation mutants. These results are the first to indicate that HTLV-1, an etiologic agent associated with lymphoproliferative diseases, uses a conserved accessory protein to induce T-cell activation, an antecedent to efficient viral infection.

Original languageEnglish (US)
Pages (from-to)11027-11039
Number of pages13
JournalJournal of virology
Issue number20
StatePublished - Oct 2003


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