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.
Full text not available from this repository.
View at publisher
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|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||05 Mar 2012 15:52|
|Last Modified:||28 Nov 2013 01:08|
|Publisher:||American Society for Microbiology|
|Funders:||Swiss National Science Foundation|
|Free access at:||Publisher DOI. An embargo period may apply.|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page