Inhibition of human T cell leukemia virus type 2 (HTLV-2) replication by the suppressive action of class II transactivator and nuclear factor Y

The master regulator of MHC-II gene transcription, class II transactivator
(CIITA), acts as a potent inhibitor of human T cell leukemia
virus type 2 (HTLV-2) replication by blocking the activity of the viral
Tax-2 transactivator. Here, we show that this inhibitory effect
takes place at the nuclear level and maps to the N-terminal 1–321
region of CIITA, where we identified a minimal domain, from
positions 64–144, that is strictly required to suppress Tax-2 function.
Furthermore, we show that Tax-2 specifically cooperates with
cAMP response element binding protein-binding protein (CBP) and
p300, but not with p300CBP-associated factor, to enhance transcription
from the viral promoter. This finding represents a unique
difference with respect to Tax-1, which uses all three coactivators
to transactivate the human T cell leukemia virus type 1 LTR. Direct
sequestering of CBP or p300 is not the primary mechanism by which
CIITA causes suppression of Tax-2. Interestingly, we found that the
transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation.
Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.