ID: 214. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Chukwurah, Evelyn; Radetskyy, Roman; Daher, Aicha; Gatignol, Anne; Patel, Rekha C.
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 104
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.218
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">During the course of infection, HIV uses various measures to counter the host cell's antiviral response. One such mechanism is directed against the interferon (IFN)-induced kinase, Protein Kinase R (PKR). In the presence of viral RNAs, PKR is activated and phosphorylates the translation initiation factor, eIF2<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7rms" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e106" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">α</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>. This shuts down the synthesis of both host and viral proteins, allowing the cell to mount an effective anti-viral response or trigger apoptosis if the infection cannot be overcome. PKR is also activated by the cellular protein, PACT. Recent studies have indicated that during HIV infection, PACT's interactions with PKR become inhibitory, due in part to its increased interactions with Adenosine Deaminase Acting on RNA (ADAR1). Using various reporter systems as well as in vitro kinase assays, we have shown that interactions between PACT, ADAR1, and viral factors are necessary to diminish the activation of PKR in response to HIV infection. Our results highlight a centrally important pathway by which HIV subverts the host cell's antiviral activities and protein interactions in order to enhance its own replication. These results also indicate that targeting this pathway by specific drugs could lead to a disruption of PACT-ADAR1-PKR interactions and result in PKR activation during viral replication to limit the viral load in infected cells.</p> </sec> </abstract>