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Journal of Virology, November 2007, p. 12427-12438, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01105-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?{triangledown}

Idoia Burgui ,1,{dagger},{ddagger} Emilio Yángüez,1,{dagger} Nahum Sonenberg,2 and Amelia Nieto1*

Centro Nacional de Biotecnología, CSIC Darwin 3, Cantoblanco 28049, Madrid, Spain,1 Department of Biochemistry, and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada2

Received 22 May 2007/ Accepted 30 August 2007

Influenza virus mRNAs bear a short capped oligonucleotide sequence at their 5' ends derived from the host cell pre-mRNAs by a "cap-snatching" mechanism, followed immediately by a common viral sequence. At their 3' ends, they contain a poly(A) tail. Although cellular and viral mRNAs are structurally similar, influenza virus promotes the selective translation of its mRNAs despite the inhibition of host cell protein synthesis. The viral polymerase performs the cap snatching and binds selectively to the 5' common viral sequence. As viral mRNAs are recognized by their own cap-binding complex, we tested whether viral mRNA translation occurs without the contribution of the eIF4E protein, the cellular factor required for cap-dependent translation. Here, we show that influenza virus infection proceeds normally in different situations of functional impairment of the eIF4E factor. In addition, influenza virus polymerase binds to translation preinitiation complexes, and furthermore, under conditions of decreased eIF4GI association to cap structures, an increase in eIF4GI binding to these structures was found upon influenza virus infection. This is the first report providing evidence that influenza virus mRNA translation proceeds independently of a fully active translation initiation factor (eIF4E). The data reported are in agreement with a role of viral polymerase as a substitute for the eIF4E factor for viral mRNA translation.

* Corresponding author. Mailing address: Centro Nacional de Biotecnología, CSIC Cantoblanco, 28049 Madrid, Spain. Phone: 34915854914. Fax: 34915854506. E-mail: anmartin{at}cnb.uam.es

{triangledown} Published ahead of print on 12 September 2007.

{dagger} I.B. and E.Y. contributed equally to this work.

{ddagger} Present address: Centro de Investigaciones Biológicas, CSIC Ramiro de Maeztu 9, 28040 Madrid, Spain.

Journal of Virology, November 2007, p. 12427-12438, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01105-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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