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A CRISPR knockout mouse library for functional genomics in influenza research
Hiroshi Ueki1, Yuriko Tomita2, Calvin Duong3
1The University of Tokyo, Pandemic Preparedness, Infection and Advanced Research Center, Tokyo 108-8639, Japan; International Virus Infectious Disease Research Center, National Institute of Global Health and Medicine, Japan Institute for Health Security (JIHS), Tokyo 162-8655, Japan; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Researchers developed a mouse model system to identify host factors influencing influenza A virus infection. This study identified 17 new host factors that, when removed, make mice resistant to the flu virus.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Validating host factors for viral diseases in animal models is challenging.
- This limits understanding of viral life cycles and disease development.
Purpose of the Study:
- To create a screening platform for identifying host factors in influenza A virus infection.
- To overcome limitations in translating in vitro findings to whole-animal models.
Main Methods:
- Developed a screening platform using 84 CRISPR-Cas9 gene-modified mouse lines.
- Targeted host factors identified from literature and in vitro studies.
- Screened for resistance to influenza A virus infection.
Main Results:
- Identified 17 host factors conferring resistance to influenza A virus upon genetic ablation.
- Detailed studies on Arhgef28 and Lasp1 revealed distinct protective mechanisms.
- Established a valuable resource for studying virus-host interactions.
Conclusions:
- The developed mouse library is a powerful platform for in vivo host factor screening.
- Provides a physiologically relevant context for understanding influenza A virus pathogenesis.
- Facilitates the discovery of novel antiviral targets.
