The MHC class II transactivator is a strong physiologic antagonist of HIV-1 replication

The expression of the MHC class-II transactivator (CIITA)
whose locus AIR-1 and corresponding function were discovered
in our laboratory, is needed for continuous expression of MHC
class-II molecules and consequent antigen presenting function by
APC. Unexpectedly, and of great relevance for antiviral functions,
we found that CIITA potently inhibits HIV-1 viral replication
by a competitive action on the viral transactivator Tat for
Cyclin T1, the cellular cofactor used by Tat to elongate viral
transcripts. This effect is found in APC and, of greater importance,
also in HIV-1-infected T cells. Molecular analysis has
revealed that the inhibitory activity of CIITA for HIV-1 Tat
maps to the N-terminal region, and particularly to the segment
200–285 included within the P/S/T region of the CIITA activation
domain which is then the molecularly defined Cyclin-T1-interacting
region. Thus CIITA has a dual role on HIV infection: 1)- it
increases APC function for HIV-1 viral antigens; 2)- it decreases
viral replication and thus viral spreading in infected individuals.
Within this frame CIITA represents an ideal molecule to control
both innate and adaptive immunity against the virus.
Considering the functional importance of a sustained and persistent
expression of CIITA in APC, the search for potential synthetic
and natural mediators, drugs and biomolecules, that can
act on CIITA expression at level of transcription as well as
biosynthesis, will be of great importance in tailoring better vaccines
against HIV-1, and in controlling and combating HIV-1
infection and spreading.