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SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening

  • Tiezhu Liu
  • Jiajia Li
  • Yang Liu
  • Yuanyuan Qu
  • Aqian Li
  • Chuan Li
  • Quanfu Zhang
  • Wei Wu
  • Jiandong Li
  • Yan Liu
  • Dexin Li
  • Shiwen WangEmail author
  • Mifang LiangEmail author
Research Article

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome (SFTS) in humans. The molecular mechanisms and host cellular factors required for SFTSV infection remain uncharacterized. Using a genome-wide CRISPR-based screening strategy, we identified a host cellular protein, sorting nexin 11 (SNX11) which is involved in the intracellular endosomal trafficking pathway, as an essential cell factor for SFTSV infection. An SNX11-KO HeLa cell line was established, and SFTSV replication was significantly reduced. The glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum (ER) or Golgi apparatus. pH values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells, and lysosomal-associated membrane protein 1 (LAMP1) expression was significantly elevated in the SNX11-KO cells. Overall, these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11. Our study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting, membrane fusion, and other endocytic machinery.

Keywords

CRISPR screen Severe fever with thrombocytopenia syndrome virus (SFTSV) Host factor Sorting nexin 11 (SNX11) 

Notes

Acknowledgements

This work was supported by the National Key Project for Infectious Disease from the Ministry of Science and Technology (Grant No. 2018ZX10711-001).

Author Contributions

TL performed the experiments and wrote the paper; Jiajia Li, YL, and YQ performed the experiments; AL, QZ, CL, WW, YL, and Jiandong Li contributed reagents/materials/analysis tools. Jiajia Li, TL, ML, YL, Jiandong Li, and DL analyzed and discussed the data. ML and SW designed the project and edited the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

12250_2019_141_MOESM1_ESM.pdf (560 kb)
Supplementary material 1 (PDF 560 kb)

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Copyright information

© Wuhan Institute of Virology, CAS 2019

Authors and Affiliations

  1. 1.Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of People’s Republic of China, National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina
  2. 2.CDC-WIV Joint Research Center for Emerging Diseases and BiosafetyWuhanChina
  3. 3.Department of MicrobiologyAnhui Medical UniversityHefeiChina
  4. 4.The First Affiliated Hospital of Anhui Medical UniversityHefeiChina

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