We describe how CIITA exerts a dual role against retroviral
infection. The first, classical role is the upregulation of MHC
class II expression and thus the capacity to present viral antigens
to CD4+ T cells. The other, evolutionary new and fundamental
role is to inhibit viral replication by blocking specifically the
function of the viral transactivators. HIV-1 Tat is inhibited
through the competition for cyclin T1 of the P-TEFb complex,
whereas HTLV-2 Tax-2 is inhibited through a concerted action
which may increase the binding affinity of the CIITA-NFY
complex for Tax-2, displacing it from the viral LTR promoter. As
expected, two distint sequences in the N-term region of CIITA
mediate the inhibitory action on Tat and Tax-2, respectively. Of
note, Tax-1 from HTLV-1 seems also to be inhibited by the same
sequence that inhibits HTLV-2 Tax-2. Interestingly, only those
CIITA fragments containing the minimal inhibitory domains that
localize into the nucleus could exert an effective suppressive
action. Taken together, our results indicate that CIITA is an
extant molecular tool endowed with distinct evolving functions
against retroviruses. These distinct properties of CIITA will
shed new light on the molecular mechanisms of adaptive
coevolution of hosts and pathogens and may be exploited to
envisage novel therapeutic strategies aimed at counteracting
retroviral infections
