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SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening.
Tiezhu Liu1, Jiajia Li2,3, Yang Liu1
1Key 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.
Sorting nexin 11 (SNX11) is crucial for Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) infection. SNX11 facilitates viral entry into host cells by regulating endosomal trafficking, making it a potential therapeutic target.
Area of Science:
- Virology
- Cell Biology
- Infectious Diseases
Background:
- Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) causes lethal human infections.
- The molecular mechanisms and host factors governing SFTSV infection are largely unknown.
Purpose of the Study:
- To identify host cellular factors essential for SFTSV infection.
- To elucidate the role of identified factors in the viral life cycle.
Main Methods:
- Genome-wide CRISPR-based screening was employed to identify host factors.
- An SNX11-knockout (KO) HeLa cell line was generated and characterized.
- Viral glycoprotein localization, endosomal pH, and LAMP1 expression were analyzed.
Main Results:
- Sorting nexin 11 (SNX11) was identified as an essential host factor for SFTSV infection.
- SFTSV replication was significantly reduced in SNX11-KO cells.
- SNX11 deficiency blocked SFTSV penetration from endolysosomes into the cytoplasm, altering endosomal pH and LAMP1 expression.
Conclusions:
- SNX11 plays a critical role in the intracellular trafficking and penetration of SFTSV.
- The findings highlight SNX11's involvement in viral protein sorting and endocytic machinery, offering potential therapeutic targets.
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