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Downregulation of protein kinase PKR activation by porcine reproductive and respiratory syndrome virus at its early stage infection

文献类型： 外文期刊

作者： Xiao, Yueqiang 1 ; Ma, Zexu 1 ; Wang, Rong 1 ; Yang, Liping 1 ; Nan, Yuchen 1 ; Zhang, Yan-Jin 1 ;

作者机构： 1.Univ Maryland, Mol Virol Lab, VA MD Reg Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA

2.Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA

3.Shandong Acad Ag

关键词： Protein kinase PKR;PKR inhibition;Porcine reproductive and respiratory syndrome virus (PRRSV);Pulmonary alveolar macrophages (PAMs);eIF2 alpha;Innate immunity

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.293； 五年影响因子：3.599 ）

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收录情况： SCI

摘要： The interferon-induced double-strand RNA activated protein kinase (PKR) plays an important role in antiviral response. The objective of this study was to assess the effect of porcine reproductive and respiratory syndrome virus (PRRSV) on PKR activation. Here we report that PRRSV inhibited PKR activation during its early stage infection of primary pulmonary alveolar macrophages (PAMs). PRRSV infection led to lower level of phosphorylated PKR in comparison with mock-infected cells. The PKR inhibition was sustained until 10 h post infection in the presence of polyl:C, a synthetic analog of double stranded RNA activating PKR. PKR-mediated phosphorylation of the eukaryotic translation initiation factor eIF2 alpha was also lower in the PRRSV-infected PAMs during the early stage infection. Interestingly, inactivated PRRSV was capable to inhibit the PKR activation until 6 h post infection. This suggests that structural components of PRRSV virions were responsible for the inhibition, although PRRSV replication was needed for longer inhibition. These results indicate that the downregulation of PKR activation during early infection stage should be essential for PRRSV to avoid the antiviral response to initiate replication. This finding contributes to our understanding on PRRSV interaction with host innate immune response and reveal a target for control of PRRSV infection. (C) 2016 Elsevier B.V. All rights reserved.

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