Mutations in a Highly Conserved Motif of nsp1? Protein Attenuate the Innate Immune Suppression Function of Porcine Reproductive and Respiratory Syndrome Virus

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Show simple item record Li, Yanhua Shyu, Duan-Liang Shang, Pengcheng Bai, Jianfa Ouyang, Kang Dhakal, Santosh Hiremath, Jagadish Binjawadagi, Basavaraj Renukaradhya, Gourapura J. Fang, Ying 2017-04-07T16:53:54Z 2017-04-07T16:53:54Z
dc.description Citation: Li Y, Shyu D-L, Shang P, Bai J, Ouyang K, Dhakal S, Hiremath J, Binjawadagi B, Renukaradhya GJ, Fang Y. 2016. Mutations in a highly conserved motif of nsp1? protein attenuate the innate immune suppression function of porcine reproductive and respiratory syndrome virus. J Virol 90:3584–3599. doi:10.1128/JVI.03069-15.
dc.description.abstract Porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1? (nsp1?) is a multifunctional viral protein, which is involved in suppressing the host innate immune response and activating a unique ?2/?1 programmed ribosomal frameshifting (PRF) signal for the expression of frameshifting products. In this study, site-directed mutagenesis analysis showed that the R128A or R129A mutation introduced into a highly conserved motif (123GKYLQRRLQ131) reduced the ability of nsp1? to suppress interferon beta (IFN-?) activation and also impaired nsp1?'s function as a PRF transactivator. Three recombinant viruses, vR128A, vR129A, and vRR129AA, carrying single or double mutations in the GKYLQRRLQ motif were characterized. In comparison to the wild-type (WT) virus, vR128A and vR129A showed slightly reduced growth abilities, while the vRR129AA mutant had a significantly reduced growth ability in infected cells. Consistent with the attenuated growth phenotype in vitro, pigs infected with nsp1? mutants had lower levels of viremia than did WT virus-infected pigs. Compared to the WT virus in infected cells, all three mutated viruses stimulated high levels of IFN-? expression and exhibited a reduced ability to suppress the mRNA expression of selected interferon-stimulated genes (ISGs). In pigs infected with nsp1? mutants, IFN-? production was increased in the lungs at early time points postinfection, which was correlated with increased innate NK cell function. Furthermore, the augmented innate response was consistent with the increased production of IFN-? in pigs infected with mutated viruses. These data demonstrate that residues R128 and R129 are critical for nsp1? function and that modifying these key residues in the GKYLQRRLQ motif attenuates virus growth ability and improves the innate and adaptive immune responses in infected animals.
dc.rights © 2016, American Society for Microbiology. This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.title Mutations in a Highly Conserved Motif of nsp1? Protein Attenuate the Innate Immune Suppression Function of Porcine Reproductive and Respiratory Syndrome Virus
dc.type Article 2016
dc.citation.doi 10.1128/JVI.03069-15
dc.citation.issn 0022-538X
dc.citation.issue 7
dc.citation.jtitle Journal of Virology
dc.citation.volume 90
dc.contributor.authoreid jbai
dc.contributor.authoreid yfang
dc.contributor.kstate Li, Yanhua
dc.contributor.kstate Shang, Pengcheng
dc.contributor.kstate Bai, Jianfa
dc.contributor.kstate Fang, Ying

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