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Abstract
INTERFERON REGULATORY FACTORS REGULATE ACTIVATION OF HIV-1 VIA PHYSICAL AND FUNCTIONAL INTERACTIONS WITH TAT
BATTISTINI A, SGARBANTI M, BORSETTI A, MOSCUFO N, MARZIALI G, COCCIA E, ENSOLI B
Background: Transcription of the human immunodeficiency virus type 1 (HIV-1) is controlled by the cooperation of virally-encoded and host regulatory proteins. The Tat protein is the transcriptional activator of HIV-1 gene expression and essential for viral replication. However, expression of Tat after virus entry requires HIV-1 promoter activation. A sequence containing a binding site for transcription factors of the Interferon Regulatory Factors (IRF) family has been recently identified downstream of the 5’ HIV-1 LTR, and it appears be critical in HIV-1 transcription and replication. We sought to investigate the role of these cellular transcription factor in HIV-1 replication.
Methods: Functional and physical interactions between IRFs and the Tat protein were investigated by transient transcription of HIV-1 LTR CAT and vectors expressing IRF-1, -3, -7 or –4, alone or in combination with Tat. GST pull down experiments and the two hybrid system were used to demonstrate direct physical interaction between Tat and IRFs binds replication in cells expressing IRFs was tested by RT-PCR of spleed and unspleed viral in RNAs.
Results: We show that IRF-1 binds and activates the HIV-1 LTR transcription in a dose-dependent fashion. IRF-1 is produced early upon virus entry, prior to expression of Tat and cooperates with Tat in increasing virus gene transcription and replication. This cooperation depends on a direct physical interaction between IRF-1 and Tat and it is blocked by overexpression of IRF-8, the natural repressor of IRF-1. IRF-8 inhibits virus replication by displacing Tat-IRF-1 interaction on the HIV-1-LTR.
Conclusions: Our results identify IRF-1 as a cellular transcription factor essential for efficient HIV-1 gene expression and viral replication and indicate that the recruitment of IRF-1 to the HIV-1 promoter can be a key step in the early phases of infection or during viral reactivation from latency, in response to both viral infection and cell activation signals.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
121
Suggested Citation
"BATTISTINIA, et al.
INTERFERON REGULATORY FACTORS REGULATE ACTIVATION OF HIV-1 VIA PHYSICAL AND FUNCTIONAL INTERACTIONS WITH TAT.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
121"
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