Below is the abstract of the paper published from Dr. Cron's laboratory in the September 15 issue of the Journal in Immunology, which was highlighted "In This Issue".
HIV-1 preferentially replicates in activated CD4+ T cells that produce Th2 cytokines, but the mechanism driving this preference is not understood. Zhang et al. (p. 2746) hypothesized that Th2-specific transcription factors such as c-maf might drive HIV-1 replication. Single-cell level analysis of human CD4+ T cells in vitro confirmed that IL-4–producing cells preferentially promoted HIV-1 replication and long terminal repeat (LTR)-directed transcription. This preferential replication was not related to chemokine receptor expression, viral tropism, or differences in apoptosis between Th1 and Th2 cells. Instead, the transcription factor c-maf was found to specifically bind to the HIV-1 proximal LTR near the NF-κB and NFAT binding sites. These sites of the HIV-1 LTR were preferentially bound by NFAT2 and NF-κB p65, but not NFAT1 or NF-κB p50. Together with c-maf, NFAT2 and NF-κB p65 cooperatively enhanced transcription at both the IL-4 promoter and the HIV-1 LTR. Small interfering RNA-mediated depletion of c-maf impaired the transcription of both IL-4 and HIV-1 LTR. These results were upheld in primary CD4+ T cells by the observation that the three transcription factors cooperatively augmented HIV-1 expression. These data enhance our understanding of the mechanisms responsible for HIV-1 disease progression and present c-maf as a potential target for therapies aimed at slowing viral replication.