The HLA class II transcriptional activator blocks the function of HIV-1 Tat and inhibits viral replication

The expression of HLA class II genes is under the control of a transcriptional activator, CIITA,
encoded by the AIR-1 locus. Here we show that CIITA inhibits HIV-1 LTR transactivation
mediated by Tat. The inhibition occurred when CIITA and Tat were transiently expressed in
cells after transfection and, most importantly, when tat cDNA was transfected in cells
expressing CIITA in a constitutive fashion and at physiological levels. Furthermore, CIITA
inhibited the HIV-1 LTR transactivation mediated by extracellular Tat protein. CIITA inhibition
of Tat function could be reversed by overexpression of Cyclin T1, the cellular cofactor used
by Tat to facilitate elongation of viral transcripts. CIITA inhibition of Tat function had a dramatic
effect on HIV-1 productive infection of human T cells because CIITA+ T cells supported
very poorly, if any, viral replication. These results indicate that sustained expression of CIITA
in HIV-1-susceptible targets may down-regulate viral expression both in cells actively replicating
the virus and in silently infected cells requiring exogenous Tat to reactivate virus from
latency.