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Wisskirchen, C; Ludersdorfer, T H; Müller, D A; Moritz, E; Pavlovic, J (2011). The cellular RNA helicase UAP56 is required for prevention of double-stranded RNA formation during influenza A virus infection. Journal of Virology, 85(17):8646-8655.

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Abstract

The cellular DEAD box RNA helicase UAP56 plays a pivotal role in the efficient transcription/replication of
influenza A virus. UAP56 is recruited by the nucleoprotein (NP) of influenza A viruses, and recent data
revealed that the RNA helicase is required for the nuclear export of a subset of spliced and unspliced viral
mRNAs. The fact that influenza viruses do not produce detectable amounts of double-stranded RNA (dsRNA)
intermediates during transcription/replication suggests the involvement of cellular RNA helicases. Hence, we
examined whether the RNA-unwinding activity of UAP56 or its paralog URH49 plays a role in preventing the
accumulation of dsRNA during infection. First, our data showed that not only UAP56 but also its paralog
URH49 can interact with NPs of avian and human influenza A viruses. The small interfering RNA (siRNA)-
mediated depletion of either RNA helicase reduced the transport of M1 and hemagglutinin (HA) mRNAs and,
to a lesser extent, NP and NS1 mRNAs into the cytoplasm. Moreover, we found that virus infection of
UAP56-depleted cells leads to the rapid accumulation of dsRNA in the perinuclear region. In parallel, we
observed a robust virus-mediated activation of dsRNA-dependent protein kinase R (PKR), indicating that the
cellular RNA helicase UAP56 may be recruited by influenza virus to prevent dsRNA formation. The accumulation
of dsRNA was blocked when actinomycin D or cycloheximide was used to inhibit viral transcription/
replication or translation, respectively. In summary, we demonstrate that UAP56 is utilized by influenza A
viruses to prevent the formation of dsRNA and, hence, the activation of the innate immune response.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:September 2011
Deposited On:05 Mar 2012 16:52
Last Modified:28 Nov 2013 02:08
Publisher:American Society for Microbiology
ISSN:0022-538X
Funders:Swiss National Science Foundation
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1128/JVI.02559-10
PubMed ID:21680511
Citations:Web of Science®. Times Cited: 7
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