title: Biogenesis of non-structural protein 1 (nsp1) and nsp1-mediated type I interferon modulation in arteriviruses.
abstract: Type I interferons (IFNs-α/β) play a key role for the antiviral state of host, and the porcine arterivirus; porcine reproductive and respiratory syndrome virus (PRRSV), has been shown to down-regulate the production of IFNs during infection. Non-structural protein (nsp) 1 of PRRSV has been identified as a viral IFN antagonist, and the nsp1α subunit of nsp1 has been shown to degrade the CREB-binding protein (CBP) and to inhibit the formation of enhanceosome thus resulting in the suppression of IFN production. The study was expanded to other member viruses in the family Arteriviridae: equine arteritis virus (EAV), murine lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV). While PRRSV-nsp1 and LDV-nsp1 were auto-cleaved to produce the nsp1α and nsp1β subunits, EAV-nsp1 remained uncleaved. SHFV-nsp1 was initially predicted to be cleaved to generate three subunits (nsp1α, nsp1β, and nsp1γ), but only two subunits were generated as SHFV-nsp1αβ and SHFV-nsp1γ. The papain-like cysteine protease (PLP) 1α motif in nsp1α remained inactive for SHFV, and only the PLP1β motif of nsp1β was functional to generate SHFV-nsp1γ subunit. All subunits of arterivirus nsp1 were localized in the both nucleus and cytoplasm, but PRRSV-nsp1β, LDV-nsp1β, EAV-nsp1, and SHFV-nsp1γ were predominantly found in the nucleus. All subunits of arterivirus nsp1 contained the IFN suppressive activity and inhibited both interferon regulatory factor 3 (IRF3) and NF-κB mediated IFN promoter activities. Similar to PRRSV-nsp1α, CBP degradation was evident in cells expressing LDV-nsp1α and SHFV-nsp1γ, but no such degradation was observed for EAV-nsp1. Regardless of CBP degradation, all subunits of arterivirus nsp1 suppressed the IFN-sensitive response element (ISRE)-promoter activities. Our data show that the nsp1-mediated IFN modulation is a common strategy for all arteriviruses but their mechanism of action may differ from each other.
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA.
authors.forename: Chi Yong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Raymond R R
authors.initials: RR
authors.lastname: Rowland
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA.
authors.forename: Daewoo
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. Electronic address: dyoo@illinois.edu.
authors.forename: Dongwan
authors.initials: D
authors.lastname: Yoo
mesh_terms: D000818:Animals; D028382:Arteriviridae / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D017361:Viral Nonstructural Proteins
keywords: Arteriviridae; CBP degradation; EAV; IFN antagonism; LDV; PRRSV; SHFV; nsp1