Normal Human T Cell Growth, AIDS, and Adult T Cell Leukemia 
regulatory proteins encoded by this virus. The 
40-kDa Tax polypeptide is a potent transcrip- 
tional activator that induces both the HTLV-I LTR 
and several cellular genes, including those for IL- 
2Ra and IL-2. The induction of these various tran- 
scription units does not involve the direct bind- 
ing of Tax to target DNA sites, but rather is 
mediated through the indirect interplay of Tax 
with different sets of endogenous host transcrip- 
tion factors. Mutational studies of Tax have per- 
mitted the identification of discrete functional 
domains within this transactivator that are selec- 
tively responsible for the interactions with these 
different host factors. Furthermore, the amino- 
terminal 47 amino acids comprise two physically 
overlapping but functionally distinct domains 
that correspond to a novel zinc-binding motif and 
nuclear targeting signal. These domains both ap- 
pear required for the biological function of Tax. 
The HTLV-I Rex protein serves as an essential 
post-transcriptional regulator of HTLV-I struc- 
tural gene expression, inducing gag, pol, and 
env. The structural and enzymatic products are 
uniquely translated from unspliced {gag, pot) or 
singly spliced {env) viral mRNAs, and are re- 
quired for the assembly of fully infectious viri- 
ons. Recent studies have shown that Rex action is 
mediated through a Rex response element, a 
complex RNA stem-loop structure located within 
the 3' retroviral LTR. Mutational analysis of the 
rex gene has revealed the presence of at least two 
functional domains, one that mediates direct 
binding to its RNA response element and nu- 
clear/nucleolar localization and a second that is 
required for Rex activation. Rex appears to func- 
tion either by promoting the disassembly of spli- 
ceosomes engaging these long gag, pol, and env 
mRNAs or by activating the nuclear export of 
these incompletely spliced viral mRNAs. 
Unexpectedly, the HTLV-I Rex protein is capa- 
ble of functionally replacing the HIV-1 Rev pro- 
tein, acting through the distinct HIV-1 Rev RNA 
response element. However, consistent with 
their lack of amino acid homology. Rex binds at a 
site in the HLV-l RNA response element clearly 
distinct from that utilized by Rev. These findings 
highlight a pattern of convergent evolution in 
these two human retroviruses, whereby each em- 
ploys a strikingly similar post-transcriptional 
strategy for regulating the expression of its struc- 
tural gene products. 
Additionally, the HTLV-I Rex response element 
plays an important role in the polyadenylation of 
all HTLV-I transcripts, independent of the pres- 
ence of Rex. Specifically, folding of the RNA Rex 
response element serves to juxtapose upstream 
and downstream binding sites for essential nuclei 
polyadenylation factors, which must interact in a 
cooperative fashion to commit the HTLV-I site to 
effective 3' processing. Alterations of the intrinsic 
secondary structure of the interposed Rex re- 
sponse element lead to the complete loss of 3' 
end formation and correspondingly the abroga- 
tion of viral replication. 
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