Inactivation of p53 by HTLV type 1 and HTLV type 2 Tax trans-activators

Human T cell lymphotropic virus type II (HTLV-2) was originally isolated fr om a patient with a hairy T cell leukemia. It has been associated with rare cases of CD8(+) T lymphoproliferative disorders, and has a controversial r ole as a pathogen, The loss of p53 function, as a consequence of mutation o r inactivation, increases the chances of genetic damage. Indeed, the import ance of p53 as a tumor suppressor is evident from the fact that over 60% of all human cancers have a mutant or inactive p53, p53 status has been exten sively studied in HTLV-1-infected cell lines. Interestingly, despite the fa ct that p53 mutations have been found in only a minority of cells, the p53 functions were found to be impaired. We have analyzed the functional activi ty of the p53 tumor suppressor in cells transformed with HTLV-2 subtypes A and B, As with HTLV-1-infected cells, abundant levels of the p53 protein ar e detected in HTLV-2 virus-infected cell lines, Using p53 reporter plasmid or induction of p53-responsive genes in response to gamma -irradiation, the p53 was found to be transcriptionally inhibited in HTLV-2-infected cells. Interestingly, although Tax-2A and -2B inactivate p53, the Tax-2A protein a ppears to inhibit p53 function less efficiently than either Tax-1 or Tax-2B in T cells, but not in fibroblasts.