Ret. Smith et al., FUNCTIONAL CONSERVATION OF HTLV-1 REX BALANCES THE IMMUNE PRESSURE FOR SEQUENCE VARIATION IN THE REX GENE, Virology, 237(2), 1997, pp. 397-403
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.