title: Downregulation of protein kinase PKR activation by porcine reproductive and respiratory syndrome virus at its early stage infection.
abstract: 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 10h post infection in the presence of polyI:C, a synthetic analog of double-stranded RNA activating PKR. PKR-mediated phosphorylation of the eukaryotic translation initiation factor eIF2α was also lower in the PRRSV-infected PAMs during the early stage infection. Interestingly, inactivated PRRSV was capable to inhibit the PKR activation until 6h 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.
authors.affiliation: Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA; Shandong Binzhou Animal Science & Veterinary Medicine Academy, Binzhou Branch of Shandong Academy of Agricultural Sciences, Binzhou, Shandong, China.
authors.forename: Yueqiang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
authors.forename: Zexu
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.affiliation: Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Nan
authors.affiliation: Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA. Electronic address: zhangyj@umd.edu.
authors.forename: Yan-Jin
authors.initials: YJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D004789:Enzyme Activation / Q000235:genetics; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000276:immunology / Q000821:virology; D010766:Phosphorylation; D011070:Poly I-C / Q000276:immunology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000201:enzymology* / Q000276:immunology; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D013552:Swine; D014779:Virus Replication / Q000502:physiology; D019892:eIF-2 Kinase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019892:eIF-2 Kinase; D011070:Poly I-C
keywords: Innate immunity; PKR inhibition; Porcine reproductive and respiratory syndrome virus (PRRSV); Protein kinase PKR; Pulmonary alveolar macrophages (PAMs); eIF2α