title: Malaria. A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion.
abstract: Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, which precludes genetic manipulation in the cell in which the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Egan
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Department of Global Health and Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL, USA.
authors.forename: Rays H Y
authors.initials: RH
authors.lastname: Jiang
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Mischka A
authors.initials: MA
authors.lastname: Moechtar
authors.affiliation: Department of Pediatrics, Harvard Medical School and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Barteneva
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Weekes
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Luis V
authors.initials: LV
authors.lastname: Nobre
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
authors.forename: Joao A
authors.initials: JA
authors.lastname: Paulo
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Frantzreb
authors.affiliation: Japanese Red Cross Kinki Block Blood Center, Osaka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tani
authors.affiliation: Japanese Red Cross Kinki Block Blood Center, Osaka, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Takahashi
authors.affiliation: Japanese Red Cross Kyushu Block Blood Center, Fukuoka, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goldberg
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Aditya S
authors.initials: AS
authors.lastname: Paul
authors.affiliation: Department of Laboratory Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
authors.affiliation: The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA.
authors.forename: David E
authors.initials: DE
authors.lastname: Root
authors.affiliation: The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA.
authors.forename: Roger C
authors.initials: RC
authors.lastname: Wiegand
authors.affiliation: The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA.
authors.forename: John G
authors.initials: JG
authors.lastname: Doench
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA. mduraisi@hsph.harvard.edu.
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism / Q000469:parasitology*; D005820:Genetic Testing; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006790:Host-Parasite Interactions / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C497483:CD44 protein, human; D018958:CD55 Antigens; D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering