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An antiviral response directed by PKR phosphorylation of the RNA helicase A

Sadler, Anthony J., Latchoumanin, Olivier, Hawkes, David, Mak, Johnson and Williams, Bryan R. G. 2009, An antiviral response directed by PKR phosphorylation of the RNA helicase A, PLoS pathogens, vol. 5, no. 2, pp. 1-11, doi: 10.1371/journal.ppat.1000311.

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Title An antiviral response directed by PKR phosphorylation of the RNA helicase A
Author(s) Sadler, Anthony J.
Latchoumanin, Olivier
Hawkes, David
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Williams, Bryan R. G.
Journal name PLoS pathogens
Volume number 5
Issue number 2
Start page 1
End page 11
Total pages 11
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2009-02
ISSN 1553-7366
1553-7374
Keyword(s) RNA
antiviral response
PKR phosphorylation
immune response
Summary The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the α subunit of the eukaryotic translation initiation factor 2 (eIF2α) to inhibit protein translation. A broad range of regulatory functions has also been attributed to PKR. However, as few additional PKR substrates have been identified, the mechanisms remain unclear. Here, PKR is shown to interact with an essential RNA helicase, RHA. Moreover, RHA is identified as a substrate for PKR, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA). Through this mechanism, PKR can modulate transcription, as revealed by its ability to prevent the capacity of RHA to catalyze transactivating response (TAR)–mediated type 1 human immunodeficiency virus (HIV-1) gene regulation. Consequently, HIV-1 virions packaged in cells also expressing the decoy RHA peptides subsequently had enhanced infectivity. The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism.
Language eng
DOI 10.1371/journal.ppat.1000311
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2009, Public Library of Science
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047595

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.