期刊
VIROLOGY
卷 433, 期 2, 页码 431-439出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2012.08.034
关键词
PRRSV; Type-1 interferon inhibition; Innate immunity; Non-structural protein 1 alpha and 1 beta
类别
资金
- USDA NRICGP [2008-00903, 2009-01654, 2012-67015-30191]
The non-structural protein 1 (nsp1) of porcine reproductive and respiratory syndrome virus is partly responsible for inhibition of type I interferon (IFN) response by the infected host. By performing alanine-scanning mutagenesis, we have identified amino acid residues in nsp1 alpha and nsp1 beta (the proteolytic products of nsp1) that when substituted with alanine(s) exhibited significant relief of IFN-suppression. A mutant virus (16-5A, in which residues 16-20 of nsp1 beta were substituted with alanines) encoding mutant nsp1 beta recovered from infectious cDNA clone was shown to be attenuated for growth in vitro and induced significantly higher amount of type I IFN transcripts in infected macrophages. In infected pigs, the 16-5A virus exhibited reduced growth at early times after infection but quickly regained wild type growth properties as a result of substitutions within the mutated sequences. The results indicate a strong selection pressure towards maintaining the IFN-inhibitory property of the virus for successful propagation in pigs. (C) 2012 Elsevier Inc. All rights reserved.
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