V3 LOOP OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REDUCES CYCLIN-E EXPRESSION AND INDUCES G(1) ARREST IN INTERLEUKIN 2-DEPENDENT T-CELLS

We previously described that V3 loop derived from the HTLV-III BH10 cl one V3-BH10 markedly suppressed IL-2-driven T cell proliferation and p roduced G(1) arrest of the cells, Here, we tested the effect of V3-BH1 0 on the molecules that are involved in transition from the G(1) to S phase of the cell cycle, The effect of V3-BH10 on the IL-2-induced exp ression of G(1) cyclins, Cdk inhibitors, and phosphorylation of retino blastoma protein (pRb) was tested by immunoblotting, using the IL-2-de pendent CD4-positive cell line Kit 225, Furthermore, IL-2-dependent ki nase activity of the cyclin E-Cdk2 complex was investigated with histo ne H1 as a substrate, V3-BH10 reduced the IL-2-dependent expression of cyclin E, but not that of cyclin D and Cdk inhibitors such as p21 and p27, As the result of reduction of cyclin E, histone H1 kinase activi ty of the cyclin E-Cdk2 complex was markedly reduced even in the-prese nce of rIL-2, followed by incomplete phosphorylation of pRb, The reduc tion in hyperphosphorylation of pRb by V3-BH10 led to G(1) arrest of t he cell cycle, Thus, V3-BH10 induced G(1) arrest in IL-2-dependent cel l cycle progression by reducing cyclin E expression, which may be one of the mechanisms underlying the dysfunction of T cells in HIV-l-infec ted people.