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Journal of Virology, February 2006, p. 1906-1914, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1906-1914.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Leader Proteinase of Foot-and-Mouth Disease Virus Inhibits the Induction of Beta Interferon mRNA and Blocks the Host Innate Immune Response

Teresa de los Santos,{dagger} Sonia de Avila Botton,{dagger},{ddagger} Rudi Weiblen,{ddagger} and Marvin J. Grubman*

Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944

Received 2 September 2005/ Accepted 23 November 2005

We have previously shown that the leader proteinase (Lpro) of foot-and-mouth disease virus (FMDV) blocks cap-dependent mRNA translation and that a genetically engineered FMDV lacking the leader proteinase coding region (A12-LLV2) is attenuated in cell culture and susceptible animals. The attenuated phenotype apparently is a consequence of the inability of A12-LLV2 to block the expression of type I interferon (IFN-{alpha}/ß) protein, resulting in IFN-induced inhibition of FMDV replication. Here we show that in addition to preventing IFN-{alpha}/ß protein synthesis, Lpro reduces the level of immediate-early induction of IFN-ß mRNA and IFN-stimulated gene products such as double-stranded RNA-dependent protein kinase R (PKR), 2',5'-oligoadenylate synthetase, and Mx1 mRNAs in swine cells. Down-regulation of cellular PKR by RNA interference did not affect wild-type virus yield but resulted in a higher yield of A12-LLV2, indicating a direct role of PKR in controlling FMDV replication in the natural host. The observation that Lpro controls the transcription of genes involved in innate immunity reveals a novel role of this protein in antagonizing the cellular response to viral infection.

* Corresponding author. Mailing address: Plum Island Animal Disease Center, USDA, ARS, NAA, P.O. Box 848, Greenport, NY 11944. Phone: (631) 323-3329. Fax: (631) 323-3006. E-mail: marvin.grubman{at}ars.usda.gov.

{dagger} T.D.L.S. and S.D.A.B. contributed equally to this work.

{ddagger} Present address: Virology Laboratory, Federal University of Santa Maria (UFSM), 97105-900 Santa Maria, RS, Brazil.

Journal of Virology, February 2006, p. 1906-1914, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1906-1914.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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