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Cellular Response to Infection

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, Sonia de Avila Botton, Rudi Weiblen, Marvin J. Grubman
Teresa de los Santos
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944
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Sonia de Avila Botton
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944
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Rudi Weiblen
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944
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Marvin J. Grubman
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944
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  • For correspondence: marvin.grubman@ars.usda.gov
DOI: 10.1128/JVI.80.4.1906-1914.2006
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ABSTRACT

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-α/β) protein, resulting in IFN-induced inhibition of FMDV replication. Here we show that in addition to preventing IFN-α/β protein synthesis, Lpro reduces the level of immediate-early induction of IFN-β 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.

  • Copyright © 2006 American Society for Microbiology
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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, Sonia de Avila Botton, Rudi Weiblen, Marvin J. Grubman
Journal of Virology Jan 2006, 80 (4) 1906-1914; DOI: 10.1128/JVI.80.4.1906-1914.2006

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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, Sonia de Avila Botton, Rudi Weiblen, Marvin J. Grubman
Journal of Virology Jan 2006, 80 (4) 1906-1914; DOI: 10.1128/JVI.80.4.1906-1914.2006
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KEYWORDS

Endopeptidases
foot-and-mouth disease virus
Gene Expression Regulation
Immunity, Innate
Interferon-beta

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