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Journal of virology2016; 91(1); doi: 10.1128/JVI.01309-16

Structural Biology of the Arterivirus nsp11 Endoribonucleases.

Abstract: Endoribonuclease (NendoU) is unique and conserved as a major genetic marker in nidoviruses that infect vertebrate hosts. Arterivirus nonstructural protein 11 (nsp11) was shown to have NendoU activity and play essential roles in the viral life cycle. Here, we report three crystal structures of porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV) nsp11 mutants. The structures of arterivirus nsp11 contain two conserved compact domains: the N-terminal domain (NTD) and C-terminal domain (CTD). The structures of PRRSV and EAV endoribonucleases are similar and conserved in the arterivirus, but they are greatly different from that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoV), representing important human pathogens in the Nidovirales order. The catalytic center of NendoU activity is located in the CTD, where a positively charged groove is next to the key catalytic residues conserved in nidoviruses. Although the NTD is nearly identical, the catalytic region of the arterivirus nsp11 family proteins is remarkably flexible, and the oligomerization may be concentration dependent. In summary, our structures provide new insight into this key multifunctional NendoU family of proteins and lay a foundation for better understanding of the molecular mechanism and antiviral drug development. Objective: Porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus are two major members of the arterivirus family. PRRSV, a leading swine pathogen, causes reproductive failure in breeding stock and respiratory tract illness in young pigs. Due to the lack of a suitable vaccine or effective drug treatment and the quick spread of these viruses, infected animals either die quickly or must be culled. PRRSV costs the swine industry around $644 million annually in the United States and almost €1.5 billion in Europe every year. To find a way to combat these viruses, we focused on the essential viral nonstructural protein 11 (nsp11). nsp11 is associated with multiple functions, such as RNA processing and suppression of the infected host innate immunity system. The three structures solved in this study provide new insight into the molecular mechanisms of this crucial protein family and will benefit the development of new treatments against these deadly viruses.
Copyright © 2016 American Society for Microbiology.
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Publication Date: 2016-12-16 PubMed ID: 27795409PubMed Central: PMC5165224DOI: 10.1128/JVI.01309-16Google Scholar: Lookup
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Summary

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The research article presents the crystal structures of nonstructural protein 11 (nsp11) which plays significant roles in the life cycle of Arteriviruses. The findings of the study could pave the way for understanding the functionality of this protein family and aid in the development of treatments for viruses such as the porcine reproductive and respiratory syndrome virus and equine arteritis virus.

Understanding the Non-Structural Protein in Arteriviruses

  • The study is centered on the endoribonuclease (NendoU), a significant genetic marker in nidoviruses. In particular, it focuses on the Arterivirus nonstructural protein 11 (nsp11) which exhibits NendoU activity and plays crucial roles in viral reproduction.
  • The team examined three crystal structures of nsp11, derived from mutants of the porcine reproductive and respiratory syndrome virus (PRRSV) and equine arteritis virus (EAV). These viruses are significant members of the arterivirus family and are known for causing severe damages in livestock.
  • The extracted structures have two conserved compact domains: the N-terminal domain (NTD) and C-terminal domain (CTD), both of which maintain their similarity and conservatism in the arterivirus but show remarkable difference from those of SARS and MERS coronaviruses.

The Role of nsp11 in the Viral Life Cycle

  • The CTD contains the catalytic center of NendoU activity, which is crucial for reproduction. Adjacent to it is a positively charged groove, another key feature in nidoviruses.
  • Interestingly, despite the nearly identical NTD, the nsp11’s catalytic region is highly flexible, and the protein’s tendency to form multi-unit structures or oligomerization appears to be dependent on concentration.
  • nsp11 is associated with multiple functions in the virus life cycle, like RNA processing and suppression of the host’s innate immunity system. These aspects make nsp11 a vital target for finding treatments against these deadly viruses.

Implications of the Study

  • The findings provide a foundation for better understanding the functionalities and molecular mechanisms of the NendoU protein family.
  • The knowledge derived from the crystal structures of nsp11 could be pivotal in the development of antiviral drugs, given the significant damage caused by the viruses in livestock, particularly swine leading to massive economic loss.

Cite This Article

APA
Zhang M, Li X, Deng Z, Chen Z, Liu Y, Gao Y, Wu W, Chen Z. (2016). Structural Biology of the Arterivirus nsp11 Endoribonucleases. J Virol, 91(1). https://doi.org/10.1128/JVI.01309-16

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 91
Issue: 1

Researcher Affiliations

Zhang, Manfeng
  • Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China.
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Li, Xiaorong
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Deng, Zengqin
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Chen, Zhenhang
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Liu, Yang
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Gao, Yina
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Wu, Wei
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.
Chen, Zhongzhou
  • Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China chenzhongzhou@cau.edu.cn.
  • State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

MeSH Terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Conserved Sequence
  • Crystallography, X-Ray
  • Endoribonucleases / chemistry
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Equartevirus / chemistry
  • Equartevirus / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Middle East Respiratory Syndrome Coronavirus / chemistry
  • Middle East Respiratory Syndrome Coronavirus / genetics
  • Middle East Respiratory Syndrome Coronavirus / metabolism
  • Models, Molecular
  • Mutation
  • Porcine respiratory and reproductive syndrome virus / chemistry
  • Porcine respiratory and reproductive syndrome virus / enzymology
  • Protein Domains
  • Protein Multimerization
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Severe acute respiratory syndrome-related coronavirus / chemistry
  • Severe acute respiratory syndrome-related coronavirus / genetics
  • Severe acute respiratory syndrome-related coronavirus / metabolism
  • Sequence Alignment
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism

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Citations

This article has been cited 25 times.
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