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Phosphorylation of HIV Tat by PKR increases interaction with TAR RNA and enhances transcription

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BioMed Central
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PMC
Keywords
  • Research
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  • Biology

Abstract

1743-422x-2-17.fm ral ss BioMed CentVirology Journal Open AcceResearch Phosphorylation of HIV Tat by PKR increases interaction with TAR RNA and enhances transcription Liliana Endo-Munoz1, Tammra Warby1, David Harrich2 and Nigel AJ McMillan*1 Address: 1Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia and 2Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, Australia Email: Liliana Endo-Munoz - [email protected]; Tammra Warby - [email protected]; David Harrich - [email protected]; Nigel AJ McMillan* - [email protected] * Corresponding author Abstract Background: The interferon (IFN)-induced, dsRNA-dependent serine/threonine protein kinase, PKR, plays a key regulatory role in the IFN-mediated anti-viral response by blocking translation in the infected cell by phosphorylating the alpha subunit of elongation factor 2 (eIF2). The human immunodeficiency virus type 1 (HIV-1) evades the anti-viral IFN response through the binding of one of its major transcriptional regulatory proteins, Tat, to PKR. HIV-1 Tat acts as a substrate homologue for the enzyme, competing with eIF2α, and inhibiting the translational block. It has been shown that during the interaction with PKR, Tat becomes phosphorylated at three residues: serine 62, threonine 64 and serine 68. We have investigated the effect of this phosphorylation on the function of Tat in viral transcription. HIV-1 Tat activates transcription elongation by first binding to TAR RNA, a stem-loop structure found at the 5' end of all viral transcripts. Our results showed faster, greater and stronger binding of Tat to TAR RNA after phosphorylation by PKR. Results: We have investigated the effect of phosphorylation on Tat-mediated transactivation. Our results showed faster, greater and stronger binding of Tat to TAR RNA after phosphorylation by PKR. In vitro phosphorylation experiments with a series of bacterial expression cons

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