COEXPRESSION OF NF-KAPPA-B REL AND SPL TRANSCRIPTION FACTORS IN HUMAN-IMMUNODEFICIENCY-VIRUS 1-INDUCED, DENDRITIC CELL T-CELL SYNCYTIA/

Productive infection of T cells with human immunodeficiency virus 1 (H IV-1) typically requires that the T cells be stimulated with antigens or mitogens, This requirement has been attributed to the activation of the transcription factor NF-KB, which synergizes with the constitutiv e transcription factor Spl to drive the HIV-1 promoter, Recently, we h ave found that vigorous replication of HIV-1 takes place in nonactivat ed memory T cells after syncytium formation with dendritic cells (DCs) , These syncytia lack activated cells as determined by an absence of s taining for Ki-67 cell cycle antigen, The expression and activity of N F-KB and Spl were, therefore, analyzed in isolated T cells and DCs fro m humans and mice, We have used immunolabeling, Western blot analysis, and electrophoretic mobility shift and supershift assays, T cells lac k active NF-KB but express Spl as expected. DCs express high levels of all known NF-KB and Rel proteins, with activity residing primarily wi thin RelB, p50, and p65, However, DCs lack Spl, which may explain the failure of HIV-1 to replicate in purified DCs, Coexpression of NF-KB a nd Spl occurs in the heterologous DC-T-cell syncytia that are induced by HIV-1. Therefore, HIV-1-induced cell fusion brings together factors that upregulate virus transcription, Since DCs and memory T cells fre quently traffic together in situ, these unusual heterologous syncytia could develop in infected individuals and lead to chronic HIV-1 replic ation without ostensible immune stimulation.