SPECIFIC INTERACTION OF HTLV TAX PROTEIN AND A HUMAN TYPE-IV NEURONALINTERMEDIATE FILAMENT PROTEIN

The human T-cell leukemia virus (HTLV) is associated with adult T cell leukemia and neurological disorders (TSP/HAM). The HTLV transcription al transactivator, Tax, is known to exert its effect through protein-p rotein interaction with several transcription factors that activate ge nes in T cell proliferation. The pathogenic mechanism in the CNS is le ss defined, Using the yeast two-hybrid system, we have identified aspe cific Tax-binding protein as the neuronal specific intermediate filame nt protein, alpha-internexin, Tax binds to the domain corresponding to the rod region of alpha-internexin, which is essential for neurofilam ent assembly, The Tare domains invoiced in binding are separable from those involved in transactivation, TxBP-1/alpha-internexin and Tax are expressed in the cytoplasm and nucleus, respectively, when expressed alone, but in coexpressing cells, colocalization of both proteins was observed in a perinuclear, punctate distribution, This in vivo interac tion also resulted in a dramatic reduction in Tax transactivation and the network formation by alpha-internexin. The specific interaction of Tax and a neuronal specific intermediate filament protein may provide a clue to the pathogenesis of TSP/HAM.