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10.3390/v12080812

http://scihub22266oqcxt.onion/10.3390/v12080812
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32731335!7472224!32731335
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suck abstract from ncbi


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pmid32731335      Viruses 2020 ; 12 (8): ä
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  • Structural and Biological Basis of Alphacoronavirus nsp1 Associated with Host Proliferation and Immune Evasion #MMPMID32731335
  • Shen Z; Yang Y; Yang S; Zhang G; Xiao S; Fu ZF; Peng G
  • Viruses 2020[Jul]; 12 (8): ä PMID32731335show ga
  • Non-structural protein 1 (nsp1) is only characterized in alphacoronaviruses (alpha-CoVs) and betacoronaviruses (beta-CoVs). There have been extensive researches on how the beta-CoVs nsp1 regulates viral virulence by inhibiting host protein synthesis, but the regulatory mechanism of the alpha-CoVs nsp1 is still unclear. Here, we report the 2.1-A full-length crystal structure of nsp1 in emerging porcine SADS-CoV and the 1.8-A full-length crystal structure of nsp1 in the highly lethal cat FIPV. Although they belong to different subtypes of alpha-CoVs, these viruses all have a bucket-shaped fold composed of six beta-sheets, similar to the crystal structure of PEDV and TGEV nsp1. Comparing the above four structures, we found that the structure of alpha-CoVs nsp1 in the same subtype was more conserved. We then selected mammalian cells that were treated with SADS-CoV and FIPV nsp1 for RNA sequencing analysis and found that nsp1 had a specific inhibitory effect on interferon (IFN) and cell cycle genes. Using the Renilla luciferase (Rluc) assay and Western blotting, we confirmed that seven representative alpha-CoVs nsp1s could significantly inhibit the phosphorylation of STAT1-S727 and interfere with the effect of IFN-I. Moreover, the cell cycle experiment confirmed that alpha-CoVs nsp1 could encourage host cells to stay in the G0/G1 phase. Based on these findings, we not only greatly improved the crystal structure data on alpha-CoVs nsp1, but we also speculated that alpha-CoVs nsp1 regulated host proliferation and immune evasion-related biological functions by inhibiting the synthesis of host proteins, thus creating an environment conducive to the virus.
  • |Alphacoronavirus/genetics/*immunology/*physiology[MESH]
  • |Amino Acid Sequence[MESH]
  • |Animals[MESH]
  • |Cats[MESH]
  • |Cell Line[MESH]
  • |Crystallography, X-Ray[MESH]
  • |G1 Phase Cell Cycle Checkpoints/physiology[MESH]
  • |Gene Expression Regulation/genetics[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Immune Evasion/*immunology[MESH]
  • |Interferon Type I/*antagonists & inhibitors[MESH]
  • |Phosphorylation[MESH]
  • |Protein Structure, Tertiary[MESH]
  • |STAT1 Transcription Factor/metabolism[MESH]
  • |Sequence Homology[MESH]
  • |Swine[MESH]
  • |Viral Nonstructural Proteins/genetics/*metabolism[MESH]


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