FUNCTIONAL CONSERVATION OF HTLV-1 REX BALANCES THE IMMUNE PRESSURE FOR SEQUENCE VARIATION IN THE REX GENE

Naturally occurring mutations in Human T-cell Leukemia Virus Type 1 (H TLV-1) Tax protein lead to loss of recognition by cytotoxic T-lymphocy tes. Most of these mutations also abolish or severely impair the trans activation function of Tax. Ninety percent of the rex gene, which enco des the viral regulator of mRNA splicing (Rex), overlaps with the tax gene. In this paper, we report that four previously described point mu tations in tax that abolished CTL recognition and activity did not alt er either the dimerisation function or the ability to export viral mRN A of the corresponding Rex proteins. Rex proteins containing two other amino acid changes were likewise functional. However, five Rex deleti on mutants, predominantly but not exclusively found in HAM/TSP patient s, had all lost these functions. We conclude that, although the Tax pr otein is subject to strong CTL-mediated selection, there are stronger functional constraints on amino acid variation in Rex. This may limit the variation in the tax/rex nucleotide sequence which results in immu ne evasion. (C) 1997 Academic Press.