Mechanisms of T-cell activation by human T-cell lymphotropic virus type I

The interactions between human T-cell lymphotropic virus type I (HTLV-I) an d the cellular immune system can be divided into viral interference with fu nctions of the infected host T cell and the subsequent interactions between the infected T cell and the cellular immune system. HTLV-I-medinted activa tion of the infected host T cell is induced primarily by the viral protein True, which Influences transcriptional activation signal transduction pathw ays, cell cycle control, and apoptosis. These properties of Tar may well ex plain the ability of HTLV-I to immortalize T cells. It is not clear, though , how HTLV-I induces T-cell transformation (interleukin-2 [IL-2] independen ce). Recent evidence suggests that Tax may promote the G(1)- to S-phase tra nsition, although this may involve additional proteins. A role for other vi ral proteins that may constitutively activate the IL-2 receptor pathway has also been suggested. By virtue of their activated state HTLV-I-infected T cells can nonspecifically activate resting, uninfected T cells via virus-me diated upregulation of adhesion molecules. This may favor viral disseminati on. Moreover; the induction of a remarkably high frequency of antiviral CD8 (+) T cells does not appear to eliminate the infection. Indeed individuals, with a high frequency of virus-specific CD8(+) T cells have a high viral lo ad indicating a state of chronic immune system stimulation Thus, while an a ctivated immune system is needed to eradicate the infection, the spread of the HTLV-I is also accelerated under these conditions. A detailed knowledge of the molecular. interactions between virus-specific CD8(+) T cells and i mmunodominant viral epitopes holds promise for the development of specific antiviral therapy.