Research Article

Haploid Genetic Screens in Human Cells Identify Host Factors Used by Pathogens

Science  27 Nov 2009:
Vol. 326, Issue 5957, pp. 1231-1235
DOI: 10.1126/science.1178955

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Abstract

Loss-of-function genetic screens in model organisms have elucidated numerous biological processes, but the diploid genome of mammalian cells has precluded large-scale gene disruption. We used insertional mutagenesis to develop a screening method to generate null alleles in a human cell line haploid for all chromosomes except chromosome 8. Using this approach, we identified host factors essential for infection with influenza and genes encoding important elements of the biosynthetic pathway of diphthamide, which are required for the cytotoxic effects of diphtheria toxin and exotoxin A. We also identified genes needed for the action of cytolethal distending toxin, including a cell-surface protein that interacts with the toxin. This approach has both conceptual and practical parallels with genetic approaches in haploid yeast.

View Full Text

Cited By...