FORMATION OF SIMIAN IMMUNODEFICIENCY VIRUS LONG TERMINAL REPEAT CIRCLES IN RESTING T-CELLS REQUIRES BOTH T-CELL RECEPTOR-DEPENDENT AND IL-2-DEPENDENT ACTIVATION

Although immunodeficiency viruses can enter resting CD4(+) T lymphocyt es, activation of T cells is required for complete viral cDNA synthesi s and transport of double-stranded viral DNA to the nucleus. Cross-lin king T cell receptors (TCRs) on resting CD4(+) T cells induces reverse transcription of full-length simian immunodeficiency virus (SIV) geno mes, but TCR engagement alone is insufficient to stimulate SIV DNA to move to the nucleus and form long terminal repeat (LTR) circles. Neith er ligation of TCR or CD28 receptors nor interleukin 2 (IL-2) alone in duces formation of LTR circles; however, the combination of TCR ligati on with either CD28 ligation or IL-2 does. Anti-IL-2 serum inhibits th e formation of LTR circles induced by cross-linking CD3 and CD28, but has no effect on the induction of increased viral reverse transcriptio n. Thus, two signals appear to be required for immunodeficiency viruse s to move to the T cell nucleus, one from the TCR to promote reverse t ranscription of the viral genome, the other through an IL-2-dependent process leading to formation of LTR circles.