Host factor transcriptional regulation contributes to preferential expression of HIV type 1 in IL-4-producing CD4 T cells.

ABSTRACT: HIV type 1 (HIV-1) replicates preferentially in IL-4-producing CD4 T cells for unclear reasons. We show increased HIV-1 expression is irrespective of viral tropism for chemokine receptors as previously suggested, but rather transcription of the HIV-1 long terminal repeat (LTR) is increased in IL-4-producing CD4 T cells. Increased expression of HIV-1 message is also confirmed in IL-4-producing CD4 T cells from HIV-1-infected individuals ex vivo. In exploring a transcriptional mechanism, we identify a novel c-maf (required for IL-4 expression) transcription factor binding site just upstream of the dual NF-?B/NFAT binding sites in the proximal HIV-1 LTR. We demonstrate that c-maf binds this site in vivo and synergistically augments HIV-1 transcription in cooperation with NFAT2 and NF-?B p65, but not NFAT1 or NF-?B p50. Conversely, small interfering RNA inhibition of c-maf reduces HIV-1 transcription in IL-4-producing T cells. Thus, c-maf increases HIV-1 expression in IL-4-producing CD4 T cells by binding the proximal HIV-1 LTR and augmenting HIV-1 transcription in partnership with NFAT2 and NF-?B p65 specifically. This has important implications for selective targeting of transcription factors during HIV-1 infection because, over the course of HIV-1 progression/AIDS, IL-4-producing T cells frequently predominate and substantially contribute to disease pathology.

SUBMITTER: Zhang M 

PROVIDER: S-EPMC3436993 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature