4.6 Article

Upstream Stimulatory Factors Regulate HIV-1 Latency and Are Required for Robust T Cell Activation

期刊

VIRUSES-BASEL
卷 15, 期 7, 页码 -

出版社

MDPI
DOI: 10.3390/v15071470

关键词

USF1; USF2; HIV-1; latency; LTR; RBF-2; transcription; T cell activation; immune; inflammation; epigenetics

类别

向作者/读者索取更多资源

HIV-1 provirus expression is regulated by the Ras signaling pathway, which is associated with T cell receptor engagement. USF2 is crucial for HIV-1 expression, while the function of USF1 is uncharacterized. USF1 and USF2 have cooperative regulation on target genes in T cells.
HIV-1 provirus expression is controlled by signaling pathways that are responsive to T cell receptor engagement, including those involving Ras and downstream protein kinases. The induction of transcription from the HIV-1 LTR in response to Ras signaling requires binding of the Ras-responsive element binding factor (RBF-2) to conserved cis elements flanking the enhancer region, designated RBE3 and RBE1. RBF-2 is composed minimally of the USF1, USF2, and TFII-I transcription factors. We recently determined that TFII-I regulates transcriptional elongation from the LTR through recruitment of the co-activator TRIM24. However, the function of USF1 and USF2 for this effect are uncharacterized. Here, we find that genetic deletion of USF2 but not USF1 in T cells inhibits HIV-1 expression. The loss of USF2 caused a reduction in expression of the USF1 protein, an effect that was not associated with decreased USF1 mRNA abundance. USF1 and USF2 were previously shown to exist predominately as heterodimers and to cooperatively regulate target genes. To examine cooperativity between these factors, we performed RNA-seq analysis of T cell lines bearing knockouts of the genes encoding these factors. In untreated cells, we found limited evidence of coordinated global gene regulation between USF1 and USF2. In contrast, we observed a high degree of genome-wide cooperative regulation of RNA expression between these factors in cells stimulated with the combination of PMA and ionomycin. In particular, we found that the deletion of USF1 or USF2 restricted T cell activation response. These observations indicate that USF2, but not USF1, is crucial for HIV-1 expression, while the combined function of these factors is required for a robust T cell inflammatory response.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据