Sterol regulatory element-binding protein 2 couples HIV-1 transcription to cholesterol homeostasis and T cell activation.

Abstract

Cholesterol plays an essential role in the life cycle of several enveloped viruses. Many of these viruses manipulate host cholesterol metabolism to facilitate their replication. HIV-1 infection of CD4(+) T cells activates the sterol regulatory element-binding protein 2 (SREBP2) transcriptional program, which includes genes involved in cholesterol homeostasis. However, the role of SREBP2-dependent transcription in HIV-1 biology has not been fully examined. Here, we identify TFII-I, a gene critical for HIV-1 transcription in activated T cells, as a novel SREBP2 target gene. We found TFII-I expression increased after HIV-1 infection or activation of human primary CD4(+) T cells. We show that inhibition of SREBP2 activity reduced TFII-I induction in response to these stimuli. More importantly, small interfering RNA (siRNA)-mediated gene silencing of either SREBP2 or TFII-I significantly reduced HIV-1 production in CD4(+) T cells. We also found that TFII-I potentiates Tat-dependent viral gene expression, consistent with a role at the level of HIV-1 transcription. Collectively, our results demonstrate for the first time that HIV-1 transcription in T cells is linked to cholesterol homeostasis through control of TFII-I expression by SREBP2.

• Authors: Harry E Taylor, Michael E Linde, Atanu K Khatua, Waldemar Popik, James E K Hildreth
• Journal: Journal of virology (J Virol) Vol. 85 Issue 15 Pg. 7699-709 (Aug 2011) ISSN: 1098-5514 [Electronic] United States
• PMID: 21613400 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• DNA Primers
• GTF2I protein, human
• SREBF2 protein, human
• Sterol Regulatory Element Binding Protein 2
• Transcription Factors, TFII
• Cholesterol

Topics

• Base Sequence
• Cell Line
• Cholesterol (metabolism)
• DNA Primers
• Flow Cytometry
• HIV-1 (genetics)
• Homeostasis (physiology)
• Humans
• Lymphocyte Activation
• Protein Binding
• Sterol Regulatory Element Binding Protein 2 (metabolism, physiology)
• T-Lymphocytes (immunology)
• Transcription Factors, TFII (genetics)
• Transcription, Genetic (physiology)