CD30 induction of human immunodeficiency virus gene transcription is mediated by TRAF2.
CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily expressed on activated T and B lymphocytes and natural killer cells. Ligation of CD30 was previously shown to induce NF-kappaB activation and HIV expression in chronically infected T lymphocytes. In this study, we report that two members of the TNFR-associated factor (TRAF) family of proteins, TRAF1 and TRAF2, independently bind to the intracellular domain of CD30 (CD30IC). Transient overexpression of TRAF2, but not TRAF1, induced NF-kappaB activation and HIV-1-long terminal repeat-driven transcription in the T cell line, KT3. Moreover, dominant negative mutants consisting of the TRAF domain of TRAF1 and TRAF2 inhibited CD30 induction of NF-kappaB activation and HIV-1 transcription. These results suggest that CD30 ligation may enhance the expression of HIV via TRAF-2-mediated activation of NF-kappaB.
Tsitsikov
E N
EN
Division of Immunology, Children's Hospital, Department of Pediatrics Harvard Medical School, Boston, MA 02115, USA.
Wright
D A
DA
Geha
R S
RS
D002460:Cell Line; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D017730:Ki-1 Antigen / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011940:Receptor Aggregation; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000821:virology; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014158:Transcription, Genetic
D017730:Ki-1 Antigen; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2