HIV-1, HTLV-1 and normal T-cell growth: transcriptional strategies and surprises

In this review, Warner Greene and colleagues discuss recent studies that have revealed an intriguing molecular interplay between two pathogenic human retroviruses, HIV-1 and HTLV-1, and certain cellular genes that normally control T-cell growth. Activation of T cells during an immune response results in the induction of select transcription factors that bind specifically to kappa B enhancer elements present in both the IL-2R alpha and IL-2 genes. Normal T-cell growth is in part regulated by the transient expression of these genes. The Tax protein of HTLV-1 induces these same kappa B-specific proteins, but in contrast to immune stimulation, HTLV-1 infection of T cells leads to constitutive IL-2R alpha gene expression and immortalization. A second human retrovirus, HIV-1, can subvert the normal action of the kappa B-binding factors induced by these immune stimuli. Rather than promoting T-cell growth, these factors may augment viral replication and promote T-cell death.