{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:58:23Z","timestamp":1792627103727,"version":"4.5.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human T-lymphotropic virus type 1 (HTLV-1) is the agent of an aggressive malignancy of CD4\n            <jats:sup>+<\/jats:sup>\n            T lymphocytes, called adult T-cell lymphoma\/leukemia, and is associated with numerous immune-mediated diseases. To establish infection, HTLV-1 must activate targeted T cells during early stages of infection. We recently demonstrated that the HTLV-1 accessory protein p12\n            <jats:sup>I<\/jats:sup>\n            is critical for persistent infection in vivo and for viral infectivity in quiescent primary lymphocytes, suggesting a role for p12\n            <jats:sup>I<\/jats:sup>\n            in lymphocyte activation. To test whether p12\n            <jats:sup>I<\/jats:sup>\n            modulates signaling pathways required for T-lymphocyte activation, we examined AP-1-, NF-\u03baB-, and nuclear factor of activated T cells (NFAT)-driven reporter gene activity in p12\n            <jats:sup>I<\/jats:sup>\n            -expressing Jurkat T cells compared to vector-transfected control cells. HTLV-1 p12\n            <jats:sup>I<\/jats:sup>\n            specifically induced NFAT-mediated transcription approximately 20-fold in synergy with the Ras\/mitogen-activated protein kinase pathway, but did not influence AP-1- or NF-\u03baB-dependent gene expression. Inhibition of calcium-dependent signals by cyclosporin A, BAPTA-AM [glycine,\n            <jats:italic>N<\/jats:italic>\n            ,\n            <jats:italic>N<\/jats:italic>\n            \u2032-1,2-ethanediylbis(oxy-2,1-phenylene)-bis-\n            <jats:italic>N<\/jats:italic>\n            -2-(acetyloxy)methoxy-2-oxoethyl]-[bis(acetyloxy)methyl ester], and a dominant negative mutant of NFAT2 abolished the p12\n            <jats:sup>I<\/jats:sup>\n            -mediated activation of NFAT-dependent transcription. In contrast, inhibition of phospholipase C-\u03b3 and LAT (linker for activation of T cells) did not affect p12\n            <jats:sup>I<\/jats:sup>\n            -induced NFAT activity. Importantly, p12\n            <jats:sup>I<\/jats:sup>\n            functionally substituted for thapsigargin, which selectively depletes intracellular calcium stores. Our data are the first to demonstrate a role for HTLV-1 p12\n            <jats:sup>I<\/jats:sup>\n            in calcium-dependent activation of NFAT-mediated transcription in lymphoid cells. We propose a novel mechanism by which HTLV-1, a virus associated with lymphoproliferative disease, dysregulates common T-cell activation pathways critical for the virus to establish persistent infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.76.7.3493-3501.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:59:40Z","timestamp":1027763980000},"page":"3493-3501","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["Activation of Nuclear Factor of Activated T Cells by Human T-Lymphotropic Virus Type 1 Accessory Protein p12\n            <sup>I<\/sup>"],"prefix":"10.1128","volume":"76","author":[{"given":"Bjo\u0308rn","family":"Albrecht","sequence":"first","affiliation":[{"name":"Center for Retrovirus Research and Department of Veterinary Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine D.","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research and Department of Veterinary Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ding","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research and Department of Veterinary Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susheela","family":"Tridandapani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine and Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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