التفاصيل البيبلوغرافية
| العنوان: |
Diversity for endoribonuclease nsp15-mediated regulation of alpha-coronavirus propagation and virulence |
| المؤلفون: |
Xie, Yunfei, Chen, Chener, Zhang, Ding, Jiao, Zhe, Chen, Yixi, Wang, Gang, Tan, Yubei, Zhang, Wanpo, Xiao, Shaobo, Peng, Guiqing, Shi, Yuejun |
| المساهمون: |
He, Biao, MOST | National Key Research and Development Program of China, MOST | NSFC | National Science Fund for Distinguished Young Scholars |
| المصدر: |
Microbiology Spectrum ; volume 11, issue 6 ; ISSN 2165-0497 |
| بيانات النشر: |
American Society for Microbiology |
| سنة النشر: |
2023 |
| الوصف: |
Endoribonuclease non-structural protein 15 (nsp15) (EndoU) is conserved among coronaviruses (CoVs) and is crucial for viral replication, evasion of the innate immune system, and virulence. EndoU-deficient CoVs can activate the interferon (IFN) response and attenuate their virulence, and nsp15 is considered the target of attenuated vaccine development. Among alpha-CoVs, transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) cause lethal diseases in piglets and cats, but the role of EndoU in viral propagation and virulence remains unclear. Here, we verified the TGEV and FIPV EndoU active sites His226 and His241 and found that the antagonization of SeV-induced IFN-β production by nsp15 depends on its EndoU activity. Furthermore, we constructed infectious clones of wild-type (WT) and EndoU-deficient (EnUmt) TGEV and FIPV. Unexpectedly, we found that both the WT and EnUmt viruses propagated efficiently in multiple types of immunocompetent (PK-15, IPI-2I, ST, CRFK, F81, and Fcwf-4) cells. Moreover, the results of infection experiments showed that compared with piglets and cats infected with the WT, the EnUmt virus-infected piglets and cats did not exhibit significantly reduced mortality, tissue injury, or viral shedding. Specially, the death of cats infected with EnUmt-FIPV occurred earlier than that of cats infected with WT. Hence, our results suggest that the function of EndoU is conserved, but nsp15-mediated regulation of the propagation and pathogenesis of CoVs are diverse. Our findings provide a reference for an in-depth understanding of EndoU-mediated immune escape and pathogenicity in CoVs. IMPORTANCE Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target discovery. Whether the EndoU activity of CoV nsp15, as a virulence-related protein, has a diverse effect on viral virulence needs to be further explored. Here, we found that the transmissible ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1128/spectrum.02209-23 |
| الإتاحة: |
https://doi.org/10.1128/spectrum.02209-23Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ ; https://journals.asm.org/non-commercial-tdm-licenseTest |
| رقم الانضمام: |
edsbas.B09CC3E7 |
| قاعدة البيانات: |
BASE |
