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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/01.qai.0000429282.45619.8c
Abstracts: PDF Only

P105 The MHC-II transactivator CIITA is a viral restriction factor against HIV-1 replication.

Forlani, Greta; Vicenzi, Elisa; Poli, Guido; Accolla, Roberto S.; Tosi, Giovanna

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Abstract

The MHC-II transactivator CIITA inhibits HIV-1 replication in human T cells by competing with the viral transactivator Tat for the binding to Cyclin T1 of PTEF-b. Here we analyzed the anti-viral function of CIITA in a monocyte-macrophage model of HIV-1 infection, the U937 promonocytic Plus and Minus clones characterized by efficient or inefficient capacity to support HIV-1 replication, respectively. We verified that U937 Minus cells express MHC-II molecules on the cell surface whereas Plus cells do not. This phenotype correlates with the expression of CIITA protein restricted only to Minus cells. Importantly, we show that Tatdependent. HIV-1 LTR transactivation is reduced in Minus cells compared to Plus cells. The stable expression of exogenous CIITA in Plus cells inhibits Tat-mediated activation of the viral LTR reverting the Plus phenotype into a Minus "like" phenotype. Accordingly, HIV-1 replication was significantly reduced in Plus-CIITA transfected cells compared to Plus parental cells. Recently, the host factor TRIM22 expressed selectively in Minus cells, but not in Plus cells, was shown to inhibit basal HIV-1 transcription. Of note, CIITA did not induce TRIM22 expression in Plus-CIITA transfectants suggesting that the two factors might act independently to counteract viral replication. Overall our findings demonstrate that CIITA acts as a viral restriction factor against HIV-1 in both T cells and monocytes, the primary cellular targets of HIV-1 infection. These results may explain previous observations on the refractory state of monocyte-macrophages to HIV-1 replication when stimulated with INF-gamma, the most potent activator of CIITA expression and may help to envisage new strategies of intervention to limit HIV-1 replication and spreading in infected hosts.

(C) 2013 Lippincott Williams & Wilkins, Inc.

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