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Hunting Viral Receptors Using Haploid Cells
Sirika Pillay1, Jan E Carette1
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305; email: sirika14@stanford.edu , carette@stanford.edu.
Annual Review of Virology
|March 10, 2016
Summary
Discovering host proteins is key to understanding viral entry. Genetic screens in haploid cells identified NPC1 and LAMP1 as crucial intracellular receptors for Ebola and Lassa viruses, revealing dynamic viral tropism.
Area of Science:
- Virology
- Genetics
- Cell Biology
Background:
- Viruses utilize host cell proteins as receptors for entry, influencing infection spread and disease.
- Understanding viral receptor usage is critical for developing antiviral strategies.
Purpose of the Study:
- To review methods for viral receptor discovery.
- To highlight the utility of forward genetic screens in human haploid cells for identifying viral receptors.
- To discuss the dynamic nature of viral receptor usage.
Main Methods:
- Review of established virus receptor discovery techniques.
- Application of forward genetic screens in human haploid cells.
- Generation of high-saturation knockout alleles for sensitive interaction studies.
Main Results:
- Forward genetic screens in haploid cells are effective for virus-host interaction studies.
- Lysosomal proteins NPC1 and LAMP1 identified as intracellular receptors for Ebola virus and Lassa virus, respectively.
- Demonstration of a dynamic viral entry mechanism involving a switch from cell surface to intracellular receptors.
Conclusions:
- Genetic knockout approaches offer a powerful tool for mapping viral receptor usage.
- Receptor dynamics are crucial for understanding the pathogenesis of viruses like Ebola and Lassa.
- Further application of genetic screens will elucidate pathways exploited by viruses.
