The leader proteinase of foot-and-mouth disease virus inhibits the induction of beta interferon mRNA and blocks the host innate immune response

被引:164
作者
de los Santos, T [1 ]
Botton, SD [1 ]
Weiblen, R [1 ]
Grubman, MJ [1 ]
机构
[1] USDA ARS, NAA, Plum Ist Anim Dis Ctr, Greenport, NY 11944 USA
关键词
D O I
10.1128/JVI.80.4.1906-1914.2006
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have previously shown that the leader proteinase (L-pro) 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/beta) protein, resulting in IFN-induced inhibition of FMDV replication. Here we show that in addition to preventing IFN-alpha/beta protein synthesis, L-pro reduces the level of immediate-early induction of IFN-beta 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 L-pro controls the transcription of genes involved in innate immunity reveals a novel role of this protein in antagonizing the cellular response to viral infection.
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页码:1906 / 1914
页数:9
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