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

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Virologica Sinica

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.

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Acknowledgements

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

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Authors and Affiliations

  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 Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China

    Tiezhu Liu, Yang Liu, Yuanyuan Qu, Aqian Li, Chuan Li, Quanfu Zhang, Wei Wu, Jiandong Li, Dexin Li, Shiwen Wang & Mifang Liang

  2. CDC-WIV Joint Research Center for Emerging Diseases and Biosafety, Wuhan, 430071, China

    Shiwen Wang & Mifang Liang

  3. Department of Microbiology, Anhui Medical University, Hefei, 230032, China

    Jiajia Li & Yan Liu

  4. The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Jiajia Li

Authors
  1. Tiezhu Liu
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  2. Jiajia Li
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  3. Yang Liu
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  4. Yuanyuan Qu
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  5. Aqian Li
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  6. Chuan Li
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  7. Quanfu Zhang
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  8. Wei Wu
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  9. Jiandong Li
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  10. Yan Liu
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  11. Dexin Li
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  12. Shiwen Wang
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  13. Mifang Liang
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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.

Corresponding authors

Correspondence to Shiwen Wang or Mifang Liang.

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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.

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Liu, T., Li, J., Liu, Y. et al. SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening. Virol. Sin. 34, 508–520 (2019). https://doi.org/10.1007/s12250-019-00141-0

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  • DOI: https://doi.org/10.1007/s12250-019-00141-0

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