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Virologie. Volume 8, Number 2, 125-41, mars-avril 2004, Revue

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Author(s) : A. Beby‐Defaux, L. Maille, G. Agius

Summary : HTLV‐1 is a retrovirus etiologically linked to adult T‐cell leukemia and the tropical spastic paraparesis\\HTLV‐1‐associated myelopathy. However, only 1 to 5% of the infected individuals will develop such a disease. The viral protein Tax, encoded by the pX region, is believed to be the key of viral pathogenesis. Tax activates transcription from the viral promoter as well as from numerous cellular genes involved in host cell proliferation through transcription factors and coactivators (CREB\\ATF, NFκB, SRF, CBP\\p300, P\\CAF). Tax is also a potent repressor either through transcriptional inhibition of genes as the β polymerase gene involved in DNA repair, or through inhibiting several proteins as p53 or p16 INK4a. Thus, Tax facilitates cellular activation and growth, inhibition of apoptosis of infected cells, inhibition of DNA repair, resulting in accumulation of DNA mutations and genetic instability. This review details the functional properties of Tax with particular focus on the mechanisms involved in its capacity to modulate cellular functions.

Keywords : HTLV1, Tax, cellular coactivator, cell cycle, genetic instability, signaling pathway