Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

Zhi Chen; Shaoning Liu; Wenbo Sun; Lei Chen; Dongwan Yoo; Feng Li; Sufang Ren; Lihui Guo; Xiaoyan Cong; Jun Li; Shun Zhou; Jiaqiang Wu; Yijun Du; Jinbao Wang

doi:10.1016/j.virol.2016.07.008

Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

Virology. 2016 Dec:499:278-287. doi: 10.1016/j.virol.2016.07.008. Epub 2016 Oct 6.

Authors

Zhi Chen¹, Shaoning Liu², Wenbo Sun¹, Lei Chen¹, Dongwan Yoo³, Feng Li⁴, Sufang Ren¹, Lihui Guo¹, Xiaoyan Cong¹, Jun Li¹, Shun Zhou⁵, Jiaqiang Wu⁶, Yijun Du⁷, Jinbao Wang⁸

Affiliations

¹ Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China.
² Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China; Shandong Institute of Veterinary Drug Quality Inspection, Shandong Key Laboratory for Quality Safety Monitoring and Risk Assessment of Animal Products, Huaicun Street No. 68, Jinan 250722, Shandong Province, China.
³ Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802, USA.
⁴ Department of Biology and Microbiology, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA.
⁵ College of marine science and engineering, Qingdao Agricultural University, Changcheng Road No. 700, Qingdao 266109, China.
⁶ Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. Electronic address: [email protected].
⁷ Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. Electronic address: [email protected].
⁸ Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100, China. Electronic address: [email protected].

PMID: 27718457
DOI: 10.1016/j.virol.2016.07.008

Abstract

The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response.

Keywords: NSP1α; Nuclear export signal (NES); PRRSV; Type I IFN.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Active Transport, Cell Nucleus
Animals
CREB-Binding Protein / genetics
CREB-Binding Protein / metabolism
Cell Nucleus / genetics
Cell Nucleus / metabolism
Cell Nucleus / virology
Cytoplasm / genetics
Cytoplasm / metabolism
Cytoplasm / virology
Interferon-beta / genetics*
Interferon-beta / metabolism
Nuclear Export Signals*
Porcine Reproductive and Respiratory Syndrome / genetics
Porcine Reproductive and Respiratory Syndrome / metabolism*
Porcine Reproductive and Respiratory Syndrome / virology
Porcine respiratory and reproductive syndrome virus / chemistry
Porcine respiratory and reproductive syndrome virus / genetics
Porcine respiratory and reproductive syndrome virus / metabolism*
Promoter Regions, Genetic
Protein Binding
Proteolysis
Swine
Viral Nonstructural Proteins / chemistry
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins / metabolism*

Substances

Nuclear Export Signals
Viral Nonstructural Proteins
Interferon-beta
CREB-Binding Protein