Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the pork industry. Nonstructural protein 1 (nsp1) is a characteristic feature of alpha- and betacoronaviruses, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses. However, the detailed structure and molecular mechanisms underlying the Alphacoronavirus nsp1 inhibition of host gene expression remain unclear. Here, we report the first full-length crystal structure of Alphacoronavirus nsp1 from PEDV. The structure displays a sixstranded β;-barrel fold in the middle of two α-helices. The core structure of PEDV nsp1 shows high similarity to those of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite its low degree of sequence homology. Using ribopuromycylation and Renilla luciferase reporter assays, we showed that PEDV nsp1 can dramatically inhibit general host gene expression. Furthermore, three motifs (amino acids [aa] 67 to 71, 78 to 85, and 103 to 110) of PEDV nsp1 create a stable functional region for inhibiting protein synthesis, differing considerably from Betacoronavirus nsp1. These results elucidate the detailed structural basis through which PEDV nsp1 inhibits host gene expression, providing insight into the development of a new attenuated vaccine with nsp1 modifications.
|Original language||English (US)|
|Journal||Journal of virology|
|State||Published - Mar 1 2018|
Bibliographical noteFunding Information:
This work was supported by the National Natural Science Foundation of China (grant no. 31722056 and 31372440), the National Key R&D Plan of China (program no. 2016YFD0500103), and the Huazhong Agricultural University Scientific & Technological Self-Innovation Foundation (program no. 2662015JQ003 and 2662017PY028).
© 2018 American Society for Microbiology.
- C terminus
- Host gene expression inhibition
- Nonstructural protein 1
- Porcine epidemic diarrhea virus