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http://purl.uniprot.org/citations/27089879http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27089879http://www.w3.org/2000/01/rdf-schema#comment"

Background

We previously demonstrated that the HLA class II transactivator CIITA inhibits HIV-1 replication in T cells by competing with the viral transactivator Tat for the binding to Cyclin T1 subunit of the P-TEFb complex. Here, we analyzed the anti-viral function of CIITA in myeloid cells, another relevant HIV-1 target cell type. We sinvestigated clones of the U937 promonocytic cell line, either permissive (Plus) or non-permissive (Minus) to HIV-1 replication. This different phenotype has been associated with the expression of TRIM22 in U937 Minus but not in Plus cells.

Methods

U937 Plus cells stably expressing CIITA were generated and HLA-II positive clones were selected by cell sorting and cloning. HLA and CIITA proteins were analyzed by cytofluorometry and western blotting, respectively. HLA-II DR and CIITA mRNAs were quantified by qRT-PCR. Tat-dependent transactivation was assessed by performing the HIV-1 LTR luciferase gene reporter assay. Cells were infected with HIV-1 and viral replication was evaluated by measuring the RT activity in culture supernatants.

Results

CIITA was expressed only in HLA-II-positive U937 Minus cells, and this was strictly correlated with inhibition of Tat-dependent HIV-1 LTR transactivation in Minus but not in Plus cells. Overexpression of CIITA in Plus cells restored the suppression of Tat transactivation, confirming the inhibitory role of CIITA. Importantly, HIV-1 replication was significantly reduced in Plus-CIITA cells with respect to Plus parental cells. This effect was independent of TRIM22 as CIITA did not induce TRIM22 expression in Plus-CIITA cells.

Conclusions

U937 Plus and Minus cells represent an interesting model to study the role of CIITA in HIV-1 restriction in the monocytic/macrophage cell lineage. The differential expression of CIITA in CIITA-negative Plus and CIITA-positive Minus cells correlated with their capacity to support or not HIV-1 replication, respectively. In Minus cells CIITA targeted the viral transactivator Tat to inhibit HIV-1 replication. The generation of Plus-CIITA cells was instrumental to demonstrate the specific contribution of CIITA in terms of inhibition of Tat activity and HIV-1 restriction, independently from other cellular factors, including TRIM22. Thus, CIITA acts as a general restriction factor against HIV-1 not only in T cells but also in myeloid cells."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.org/dc/terms/identifier"doi:10.1186/s12967-016-0853-5"xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/author"Forlani G."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/author"Poli G."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/author"Tedeschi A."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/author"Tosi G."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/author"Ghezzi S."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/author"Accolla R.S."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/author"Turrini F."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/name"J Transl Med"xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/pages"94"xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/title"The MHC-II transactivator CIITA inhibits Tat function and HIV-1 replication in human myeloid cells."xsd:string
http://purl.uniprot.org/citations/27089879http://purl.uniprot.org/core/volume"14"xsd:string
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