Npro His49 and Erns Lys412 mutations in pig bovine viral diarrhea virus type 2 synergistically enhance the cellular antiviral response
2018
Tao, Jie | Li, Benqiang | Chen, Jinghua | Zhang, Chunling | Ma, Yufei | Zhu, Guoqiang | Liu, Huili
Type I interferons are major components of the innate immune response of hosts, and accordingly, many viruses have evolved mechanisms to modulate the host response during infection. Bovine viral diarrhea virus (BVDV) nonstructural protein Nᵖʳᵒ and structural protein Eʳⁿˢ play important roles in inhibiting type I interferon. The aim of this study was to explore the epistatic effects of amino acid mutations in Nᵖʳᵒ and Eʳⁿˢ in porcine ST cells to characterize the immune response induced by BVDV-2. Plasmids with mutant amino acids His49 (H49), Glu22 (E22) in Nᵖʳᵒ, and His300 (H300), Lys412 (K412) in Eʳⁿˢ which had been changed to Alanine (A) had similar effects on type I interferon production in MDBK and ST cells, but resulted in much greater ISG15, OAS, and Mx production in ST cells. The rescued vASH/NᵖʳᵒH49EʳⁿˢK412 virus showed the best efficiency with respect to modulating antiviral cytokines, indicating that the amino acids Nᵖʳᵒ H49 and Eʳⁿˢ K412 had highly synergistic effects in abolishing the ability to inhibit type I interferon. These findings have importance practical implications owing to the increasing prevalence of BVDV infections, including persistent infections, in domestic pigs.
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