In this study, we constructed for the first time a full-length cDNA clone of pig-original bovine viral diarrhea virus 2 (BVDV-2) strain SH-28, modified the cDNA clone (pASH28) for mutant pASHΔNpro and derived virus strain vASHΔNpro by deleting the genomic region encoding the Npro polypeptide, and examined significance of protein Npro for antiviral responses in vitro. Data showed that Npro-deletion mutant virus vASHΔNpro led to significant overexpression of oligo adenylate synthetase (OAS), myxovirus-resistant protein 1 (Mx1), and ubiquitin-like protein 15 (ISG15). Data also revealed that overexpression of Npro, but not NS2 and NS3 proteins, resulted in significant down-regulation of OAS, Mx1, and ISG15 production (p ≤ 0.05) in bovine cells as well as porcine cells transfected with Npro recombinant eukaryotic expression plasmids. Npro (but not NS2 and NS3) was also found to inhibit poly(IC) from inducing production of type I interferon (IFN-I). These results indicated that protein Npro may play multiple roles in regulating antiviral response in host cells interfered by pig BVDV-2 strain, and provided useful information to understand better the mechanism of BVDV-2 persistent infection in pigs.
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The authors thank Dr. Leonard Bello (Pennsylvania University) for providing MDBK cells, MAbs D89, and Bz-53; Dr. Gregor Meyers (Federal Research Centre for Virus Diseases of Animals) for critical technical guidance; and Dr. Weiping Zhang (Kansas State University) for assistance in manuscript editing. This work was supported by Grant No. 2016YFD0500900 from the National Key Research and Development Program of China, the Priority Academic Program of Development Jiangsu High Education Institution, 948 program from Ministry of Agriculture of the People’s Republic of China (Grant No. 2011-G24), Grant No. BE2014358 from the Science and Technology Department of Jiangsu province, Grant No. 14KJA230001 from the Jiangsu High Education Basic Research, the Jiangsu Graduate Student Innovation Research Project (Grant No. CXLX12_0936), the Shanghai Sailing Program (15YF1410300), and the Shanghai Agricultural Commission key project (No. 2016-1-35).
Edited by Keizo Tomonaga.
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Tao, J., Liao, J., Wang, J. et al. Pig BVDV-2 non-structural protein (Npro) links to cellular antiviral response in vitro. Virus Genes 53, 233–239 (2017). https://doi.org/10.1007/s11262-016-1410-2
- Infectious cDNA clone
- Non-structural protein
- Antiviral response